In Loving Memory of Tatiana Gomez (1980-2007)

It is hard to blog with a broken-heart and so for the past few weeks I have been unable to summon the emotional energy to contribute to the blog as much as I have desired.

On Thanksgiving morning (November 22, 2007), Tatiana Gomez, a kind hearted, gentle and caring young woman was tragically killed in an accident while driving an ATV in Fairfax, VA. Tatiana had served as the IVF and Donor Ova Coordinator at Dominion Fertility for the past several years.

All of us at Dominion were shocked and dismayed to hear of Tatiana’s death. Personally, her death has left me numb from disbelief. Those who knew Tatiana, often described her as an “angel.” She was that…and much more.

We grieve along with her family over this bright light that has passed out of our lives much too soon. I will miss her bright smile, her positive attitude and her great dedication to our patients.

Tatiana, we love you and will always keep you in our hearts.

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Progesterone: shots vs suppositories

I really think that most doctors are actually afraid of shots. I remember as a Duke medical student the scene during my first year when we were all lined up to get our hepatitis vaccines….what a bunch of weenies. Boy, we were shaking in our boots over a stupid little shot. Of course, now I am on the other side of the needle.

So why do we use the barbaric progesterone in oil shots after IVF or for an FET or donor egg cycle? Honestly, there is no really satisfactory answer. We know that progesterone suppositories work as well and yet we have a hard time using them as first line progesterone replacement. I am as guilty as the next RE in this behavior. However, I have no problem using non-injectible forms of progesterone if needed.

Fortunately, hope may be on the horizon. Ferring has a new FDA approved vaginal progesterone tablet called Endometrin. Preliminary data looks good and patient acceptance is high. On the other hand, we thought that Crinone Progesterone Gel would be the answer to the prayers of thousands of IVF patients and that did not work out so well as some patients ended up having this lump of gel extrude from their vagina after a couple of doses. Needless to say, patient compliance suffered.

So here is today’s Question of the Day (which has ended up becoming more like the Question of the Week…but hey, it’s free).

65. I had an allergic reaction to the progesterone in oil shots. Does this mean that I cannot do IVF?


Following follicle aspiration, most clinics place patients on progesterone supplementation. The rationale behind the supplemental progesterone is that following egg collection, ovarian hormone production may be impaired because many of the hormone-producing cells are removed at the time of follicle aspiration. In addition, the use of GnRH agonists such as Lupron may diminish ovarian steroid production following egg collection. Progesterone supplementation has evolved over the years to include patients undergoing both stimulated IUI cycles and IVF. Although most clinics tend to use progesterone-in-oil injections, excellent pregnancy rates have been reported in patients who used vaginal progesterone supplementation. Because the progesterone shots are either sesame or peanut oil based, allergic reactions are not infrequent; switching patients to vaginal progesterone preparations usually resolves the problem. Another strategy to maintain progesterone production after IUI or egg collection involves the use of HCG booster shots to enhance steroid production from the patient’s ovaries rather than relying on an outside source. Unfortunately, the use of HCG boosters may also increase the woman’s risk of ovarian hyperstimulation syndrome.

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HSG vs HSC vs H2O sono...What is the difference?

Medical terminology can really give patients fits and no where is this more apparent than in the distinctions between hysterosalpingogram (HSG), hysteroscopy (HSC) and hysterosonogram (H2O sono or water sono). In fact, these three tests are very different although similar information can be gleaned from them depending upon the clinical situation. Taking an accurate medical history is so very important. We ask our patients to recount specific details of complicated medical testing and yet, personally I can’t usually remember what I had for lunch yesterday (actually I can because I have been on the Special K diet since 1/1/07!). Memory is not perfect and that is why retrieving medical records is so important. When patients are moving away from Washington DC, which happens about every 4 years or so, I always make sure that they take a complete set of records with them.

So today’s “Question of the Day” from 100 Questions and Answers about Infertility, the book that more of you faithful readers need to review on Amazon.com (hint, hint and remember my Mother always said “if you can’t say anything nice, then don’t say anything at all), tries to shed some light on this confusing trio of tests.

12. What is a hysteroscopy, and do I need one? Is it the same as a water sonogram or a hysterosalpingogram?

A hysteroscopy is an outpatient surgical procedure that is performed either to diagnose or to treat a problem within the uterine cavity. During hysteroscopy, the physician inserts a small fiber-optic telescope through the cervix and into the uterus. Either gas or liquid can be used to distend the uterus and allow the physician to directly visualize the uterine cavity. The physician may also introduce small instruments into the uterus to cut scar tissue or remove polyps or fibroids. Although diagnostic hysteroscopy can be performed in the physician’s office under local anesthesia, operative hysteroscopy requires anesthesia because of the cramping that occurs during uterine manipulation. Complications of hysteroscopy are rare but may include infection, bleeding, uterine perforation, damage to adjacent structures, and even death.

A water sonogram (hysterosonogram) is a specialized ultrasound examination performed using a transvaginal ultrasound probe. A small catheter is placed within the uterine cavity, and sterile saline is then introduced into the cavity during the sonogram to allow the physician to visualize any uterine polyps or fibroids. Usually, this kind of examination does not provide any information about the status of the fallopian tubes. Nevertheless, hysterosonograms are helpful in identifying the presence of an endometrialpolyp seen on routine sonogram or the location of a fibroid (see Figure below). They have limited benefit in evaluating uterine scar tissue and are only diagnostic (not therapeutic).

A hysterosalpingogram (HSG) is similar to a hysterosonogram in that fluid is introduced into the uterine cavity—but that is where the similarity ends. During an HSG (see Figure below), a radioopaque dye is first introduced into the uterus; x-rays are then taken of the area. The HSG can be used to diagnose polyps and fibroids and is superior to hysterosonogram in evaluating the presence of uterine scar tissue. This type of imaging also provides information on the status of the fallopian tubes, unlike either a hysteroscopy or a hysterosonogram. Because it employs traditional x-rays, an HSG is usually performed at a hospital’s radiology department or at a radiologist’s office, as few REs have this equipment in their offices.

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Who should evaluate the infertile couple?

Patients end up seeing a Reproductive Endocrinologist as a result of a multitude of factors. Some are referred by friends and co-workers. Some are sent by their primary care provider or by their Ob/Gyn. Many are self-referred and end up seeing us because of advertising, the internet or because they read this fantastic book titled “100 Questions and Answers about Infertility.” Actually, I have yet to see a patient who came running to see me because of the book, but you never know what will happen once Oprah makes it a selection for her Book Club. Since many Ob Gyns refer patients to specialists we like to maintain a good working relationship with them, but sometimes this becomes an issue when it comes to the fertility evaluation.

Although many non-REs are perfectly capable of ordering the tests appropriate to the evaluation of the infertile couple, some may not know how to interpret the findings. Hence, we will sometimes see patients who have been managed in a sub-optimal fashion. For example, many Ob Gyns will treat patients with empiric clomiphene without any monitoring or even without completing a basic assessment of the fallopian tubes or sperm quality. This approach is not appropriate.

Many studies suggest either limited or no benefit to the use of empiric clomiphene without the synergistic addition of intrauterine insemination (IUI) in these cases. However, I assume that these physicians do occasionally see patients who conceive with this approach whereas I have a biased view since I see all the patients who have failed this therapy. Remember that a Reproductive Endocrinologist deals almost exclusively with fertility issues. No pregnancy management. No sudden calls to Labor and Delivery. No Gyn cancer issues (unless it pertains to fertility preservation). No urinary incontinence. Just fertility, fertility, fertility….24/7. Why limit ourselves to this clinical problem? Well that is a topic for another day…So that leaves us with today’s Question of the Day.


5. Who should evaluate the infertile couple?


In many cases, the routine fertility evaluation can be conducted by an obstetrician/gynecologist, a family practitioner, or a reproductive endocrinologist (RE). Certain tests can easily be obtained by physicians in the first two specialties, but a reproductive endocrinologist may be required to interpret advanced testing and provide the most accurate counseling. Women who are more than 34 years old may elect to immediately consult with a reproductive endocrinologist.

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Why are we not getting pregnant?

What is the problem? That question is at the heart of most of our initial consultations and yet sometimes even after extensive testing we still are not sure why a couple is infertile. Overall, it is important to remember that infertility is a disease of couples. Often the male partner is less than enthusiastic about his role in the testing process but more than half the time male factor infertility plays a role in the couple’s situation. I always tell the wives to check with their other half and inquire if obtaining a sperm sample is painful. Because if it is, then perhaps they had better see a urologist. In 11 years of practice I have never heard back that it was…

So what are we looking for in terms of causes? Well that is the Question of the Day from 100 Questions and Answers about Infertility, the book that makes a great holiday gift.

8. What are typical causes of infertility?


The causes of infertility are wide ranging but can be examined in light of the reproductive cycle described in Question 1. (See Table 1.)


In general, the causes of infertility can be equally divided between the male and female partners in a couple. Half of all infertility cases, therefore, involve problems with the sperm of the male partner. Unfortunately, functional tests for sperm competence (the ability of sperm to fertilize an egg) are not available. Thus, when assessing male-related fertility issues, a semen analysis determines the total number of sperm (concentration), the percentage of those sperm that are moving (motility), and the shape of the sperm (morphology). Many factors can reduce the female partner’s ability to conceive. For example, a woman may have anatomical problems related to the fallopian tubes, uterus, and peritoneal structures within the pelvis such as adhesions or endometriosis. Problems with ovulation are very common in infertile patients, and women with irregular periods may suffer from a common disorder such as polycystic ovarian syndrome (PCOS). Another factor often found in conjunction with infertility is reproductive aging. A woman’s peak years of fertility occur when she is in her twenties. A woman’s fertility declines significantly during her thirties and forties, with an especially rapid decline in fertility occurring after she passes age 35.

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What is Assisted Hatching?

Older brothers can certainly torment younger ones a great deal. My brother Steven is a typical middle child. As my eldest brother (and my protector in the family), Mike, always wanted to be like our surgeon father, it fell to Steve to be the “black sheep/bad boy” of the family. Part of this mission was to torture his younger, spoiled brother…yours truly. His favorite means of torture was psychological, although physical brutality, such as making me always play goalie in games of basement street hockey, was sometimes employed. Steve would alternatively tell me that I was found in the gutter by Mom and Dad (how else to explain the fact that there was 8 and 13 years between me and Steve and Mike respectively), or that I had been hatched not born. Little did he know that we all actually hatch as blastocysts prior to implantation. Well, children do grow up and now I am pleased to report that I enjoy an excellent relationship with my former tormentor. For his part, it is hard to describe the CEO of the suburban campus of Boston Children’s Hospital as a “black sheep” especially when he can get some really great Red Sox tickets…

So how about Assisted Hatching? There is a lot of recent questions posted on my INCIID Bulletin Board about AH. We have moved to limiting hatching to a subgroup of patients and recently purchased a laser for our embryology team to use in performing hatching as opposed to using chemical means. We currently have not performed AH on blastocysts but some clinics have done this procedure especially on embryos that form blastocysts on day 6 or 7.

Here then is the Question of the Day from the book that even my brother Steve enjoyed reading: 100 Questions and Answers about Infertility.



61. I was told I need assisted hatching. What is this, and why is it done?


Dr. Gordon’s older brother Steven used to tease him by claiming that he was hatched and not born, but actually all of us do “hatch” in early embryonic life. The human embryo hatches out of the eggshell (zona pellucida) at the blastocyst stage of development. Assisted hatching involves weakening the zona to facilitate the emergence of the embryo following its transfer into the uterus after IVF. Proponents of assisted hatching suggest that it increases implantation and pregnancy rates. Assisted hatching is almost always performed chemically. In this technique, a dilute acid solution is used to dissolve the external eggshell. Some clinics, however, perform mechanical hatching, in which a slit is made in the eggshell, or even laser-assisted hatching, in which a laser is used to thin the zona. (See Figure 5 © 1995 Humananatomy® Illustrated).


There is some controversy regarding which patients benefit most from assisted hatching, and the indications for assisted hatching remain somewhat unclear. Most clinics recommend this step in cases where the female partner is older than age 37, has diminished ovarian reserve with increased levels of FSH, or is undergoing a frozen embryo transfer (FET) with previously cryopreserved embryos. Patients who have previously failed IVF following replacement of good-quality embryos may also benefit from assisted embryo hatching. The risks of assisted hatching are believed to be quite low. There have been reports of increased rates of identical twinning following mechanical hatching (but not after chemical-assisted hatching). There is no evidence that assisted hatching harms the embryo or causes any increased rate of birth defects in children.

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Can PGS improve IVF outcome?

So as we get ready for Halloween and all those cute little goblins and princesses let’s tackle the million dollar question: Does PGS improve IVF outcomes? The lunch debate between Munne and Hughes at the ASRM sought to discuss that issue. Basically, Dr. Munne presented evidence that in their hand IVF outcomes are better and miscarriage rates are lower. However, the improvement was modest and not the amazingly high pregnancy rates that one would predict. Dr. Munne also criticized the recent article from Europe in the New England Journal of Medicine that showed lower delivery rates after PGS. But still the question remains as to whether PGS is the Holy Grail (“I’ll ask him but I don’t think he’ll be very keen…you see he’s already got one”) of IVF.

Dr. Hughes presented data from a recent study of his that was very informative. In this study, Dr. Hughes analyzed embryo biopsies from PGD cases for single gene defects (like cystic fibrosis). All embryos that were biopsied were analyzed for aneuploidy and also DNA fingerprinting was done. The aneuploidy data was blinded so no one knew what it showed. Once a healthy baby was born, DNA fingerprinting allowed Dr. Hughes to go back and identify the exact embryo that resulted in the healthy baby.

So what did his data show…it showed that in 16% of the cases that resulted in a healthy baby, the aneuploidy screen would have suggested that the embryo was abnormal and should NOT be transferred! How is this possible? Read the Question of the Day from 100 Questions about Infertility and find out….Pretty scary thought for Halloween.

74. Can PGS improve outcomes after IVF?

PGS has been promoted as a means to improve the odds of a successful IVF cycle. However, a large-scale, randomized, controlled study performed in women older than age 37 failed to demonstrate an improvement in clinical outcome following its use. Although the use of PGS will likely decrease the rate of miscarriage resulting from aneuploidy (an abnormal number of chromosomes in the embryo), the overall delivery rate per IVF cycle initiated may not be increased with this technology.

For couples in whom the use of prenatal diagnosis and possible pregnancy termination are not an option, PGS may be appropriate. According to an October 2006 monograph produced by the European Society of Human Reproduction and Embryology (ESHRE), “Although widely used, PGS is still considered as an experimental procedure, and its clinical utility is not fully proven.” One limitation of PGS is that many embryos at the 6- to 8- cell stage of development are mosaics, meaning that some of these cells carry a normal complement of chromosomes while other cells are abnormal. During further embryonic development, the abnormal cells presumably end up relegated to the placenta while the normal cells produce a healthy embryo.

The high rate of mosaicism in cleavage-stage embryos raises a real concern about the accuracy of PGS. One respected geneticist has estimated a rate of misdiagnosis to be 20% with PGS. Approximately 17% of the time a normal embryo is incorrectly labeled as abnormal and discarded. Even more concerning is the 3% chance that an abnormal embryo will be labeled normal and then transferred to the uterus.

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Is PGD safe?

As Gandalf said to Frodo “Is it safe?” That is certainly an important question to examine. If we pursue PGD we certainly do not want to shoot ourselves in the foot.

First of all, how could PGD create a problem? Well there are several steps that could cause potential problems. The embryo biopsy could result in damage to the remaining cells in the embryo. The removal of 1/8th of the cells in the embryo could alter the development of the embryo. The biopsy of the embryo could result in an embryo that is less tolerant of cryopreservation (freezing). The testing on the embryo could be inconclusive or incorrect. Finally, the assumption that all 8 cells in the embryo are identical and thus representative of the reproductive potential of the entire embryo may be incorrect.

All of these concerns are reasonable and I will address them later but for now let’s see what is in the book...Here is today’s question of the day from the book that all Red Sox fans should buy ASAP: 100 Questions and Answers about Infertility.

73. How safe is PGD or PGS?

An estimated 5,000 cycles of PGD/PGS are being performed in the United States each year. Although the use of these techniques is clearly increasing, the number of PGD/PGS cycles continues to represent only a small fraction of the 100,000 IVF procedures performed annually in the United States alone. The rate of congenital anomalies and of pregnancy complications following PGD/PGS does not appear to be increased over the baseline measurements. On occasion, misdiagnosis may occur, so patients undergoing PGD/PGS are usually offered traditional prenatal diagnostic tests (chorionic villus sampling-CVS or amniocentesis) to confirm the results. The rates of misdiagnosis in PGD range from 1% to 9%. Embryos from which no diagnostic information is obtained are usually discarded rather than risk embryo transfer, although this policy varies from clinic to clinic. The other risks of PGS/PGD are the same as those associated with any cycle of IVF, including multiple pregnancy and OHSS.

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What is PGD/PGS?

What a difference a couple of weeks can make. Several weeks ago the Red Sox seemed doomed to another “close but no cigar” type of season and here they are in the World Series. Over October 12-16th the annual meeting of the ASRM was here in Washington DC. It is tough to have the meeting in one’s hometown as working while attending the daily meeting can be problematic…although not as problematic as going out at night to parties and then working the next AM. However, as a fairly boring the Eagle Scout straight arrow nice guy who prefers to be in bed a by 10 PM I really wouldn’t be able to comment about what went on after dark at the ASRM. But if you want to know if your RE behaved, please feel free to contact me and I can elaborate on all the juicy details.

One of the highlights of the meeting was a lunch debate between Santiago Munne, PhD and Marcus Hughes, MD, PhD on the topic of whether preimplantation genetic diagnosis (PGD) for aneuploidy (also known as preimplantation genetic screening (PGS)) will become standard of care in IVF. Both are excellent scientists, although I must admit that Dr. Hughes is, in my book, one of the smartest human beings on the planet. Over the next few blog posts I want to address the issue of IVF with PGD/PGS and after keeping you all (and my Mom) in suspense I will tell you about the outcome of the debate.

So please accept my humble apologies for being slow to post recently…it took me a while to recover from Club Luv at the ASRM (just kidding). Here is the latest Question of the Day from the book that is being promoted on WTOP here in Washington. How about some more 5-star reviews on Amazon ? (just thought I would ask).

72. What are PGD and PGS?


Preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS) are techniques that provide diagnostic information concerning an embryo prior to its transfer to the uterus. The vast majority of PGD and PGS procedures are performed by removing 1 or 2 cells (or blastomeres) of a 6- to 8-cell embryo on day 3 of embryo culture following IVF. These cells are rapidly analyzed, and on day 5 the unaffected embryos are selected for embryo transfer. PGD was first performed in 1989 in an effort to avoid the transfer of embryos that carried serious genetic disorders (for example, cystic fibrosis). Thus couples who undergo PGD do not have infertility but rather are at risk for passing a genetic disease to their children. A wide range of single-gene and chromosomal disorders can now be diagnosed with PGD, including autosomal recessive diseases (e.g., cystic fibrosis), X-linked recessive diseases (e.g., hemophilia, Duchenne muscular dystrophy), autosomal dominant diseases (e.g., Huntington’s disease), and chromosomal rearrangements (e.g., balanced translocations). PGS is similar to PGD, but refers to screening of embryos produced in the course of fertility treatments. Thus couples who undergo PGS include infertile patients without an underlying genetic problem. PGS is performed in an attempt to identify those embryos that are genetically abnormal so that improved embryo selection will—ideally—result in improved pregnancy rates and lower miscarriage rates.

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How many do I put back?

On the INCIID bulletin board I am often asked to comment on how many embryos to transfer. It amazes me that anyone would value the opinion of the cyber-RE over their actual RE. This decision is too important to just gloss over and give it only a passing thought. Transfer too many and we have to deal with twins…or worse. Transfer too few and the next thing you know the patient is requesting records to zip off to the RE down the street. How easy things would be if the government mandated single embryo transfer…but although that works in countries with comprehensive government supported healthcare, it seems unlikely to occur in the USA. I am not a big fan of twins and would be only too happy to never have another twin pregnancy come out of our clinic, but when patients reach the point of embryo transfer they are willing to risk a lot to get that positive beta…even a multiple pregnancy.

So here is today’s Question of the Day from the book 100 Questions and Answers about Infertility that was written on my laptop that is currently sitting in a pawn shop in PG County waiting for the police to recover it (turns out you actually cannot buy stolen good legally…even if you get a receipt!).

54. How do I decide how many embryos to transfer?

Determining the number of embryos to transfer in an IVF cycle is a crucial decision that requires careful discussion between the patient / couple and the physician. The goal of every
treatment cycle should be the delivery of a full-term, healthy, singleton baby. Although transferring more than one embryo will increase the pregnancy rate, at some point transferring additional embryos merely serves to increase the multiple pregnancy rate without altering the overall pregnancy rate.

Several European countries have eliminated all discussion of how many embryos to transfer by mandating that all patients undergo only single-embryo transfers. Whereas elective (or mandatory) single-embryo transfer has been promoted heavily throughout Europe, it has not yet received widespread acceptance in the United States. One of the major disadvantages of single-embryo transfer is that it leads to a decreased IVF pregnancy rate from the fresh cycle. Proponents of single-embryo transfer claim that the potential reduction in the overall pregnancy rate is well worth the marked reduction in the twin pregnancy rate.

Twin pregnancies can be problematic because they are associated with higher rates of preterm labor and preterm delivery. Some couples, however, may desire twins or at least regard them as a neutral outcome. This view is especially prevalent among patients who are paying for the treatment themselves (rather than it being covered by insurance) and regard twins as a “two for the price of one” outcome. As noted in Question 53, the greatest risk to the health of children following IVF is the complications related to prematurity associated with multiple births. Despite the risks associated with multiple pregnancy, couples still tell us every day that they would “love to have twins.”

The ASRM has published guidelines for making the decision of how many embryos to transfer (see Table 4). Patients who fall into the excellent prognosis category should transfer only one or two embryos, whereas those with an exceedingly poor prognosis—because of the woman’s age or multiple failed IVFs, for example—may undergo embryo transfer of five or more embryos. The most problematic decisions concern those patients who fall between these two extremes. Couples who are paying out of pocket for IVF will often pressure their RE to be more aggressive in terms of the number of embryos transferred. Of course, the expense involved in caring for premature infants is many times greater than the cost of all of the fertility procedures used to initiate those pregnancies.

The financial costs are merely one part of the picture, as caring for patients with preterm labor or premature infants is also associated with a variety of emotional, psychological, and physical costs. If multiple pregnancies occur, a multifetal selective reduction procedure can be considered. This procedure is performed at approximately 10 weeks of pregnancy and involves injecting a salt solution into one or more of the gestational sacs. The overall pregnancy loss rate following this procedure is usually less than 5%. In patients who wish to avoid a triplet gestation (but who will not consider selective reduction), it is best to limit the number of embryos transferred to one or two.

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Is Possession 9/10ths of the Law?

Readers of this blog may recall that my MacBook Pro was stolen from my car while it was parked in my driveway on a residential street in Bethesda, MD. Like a complete idiot I had left it in my unlocked car overnight and like an even bigger idiot I had not password protected the computer (huge gasp of shock from the reader). Fortunately, the computer was fully backed up just 48 hours earlier and I successfully restored all of my files (including the photo of me in my Boy Scout leader uniform which I have mercifully deleted from the blog).

Last night my son, Seth, came running downstairs and asked me to check out the weird message on my iTunes account. On my iTunes account info page my name had been changed to Marvin Dixon and my phone number had been replaced by a number that I did not recognize. This was not the first time I had seen this name. On Wed night I had received an email that listed my email account but with the name Marvin Dixon, not my name…

So I called Mr. Dixon who informed me that he had indeed purchased a MacBook Pro from a local Pawn Shop and had no idea it was stolen. Didn’t he wonder why it had all those files still on it??? Nope, he just figured someone needed the cash and sold it to the Pawn Shop. He said that he had taken it to the Mac store and they had helped him enter his name into the computer and the .Mac account! I was so pissed off at Apple if this is true. I had called repeatedly to Apple to ask if the computer could be listed as stolen based upon the serial number so that if someone took it to the Apple Store then it would send up a red flag. Not possible I was told repeatedly.

So I called the police, having previously filed a report and gave them the information about the new owner. The officer was very polite. I then asked him what happens next. Well, if Mr. Dixon did indeed purchase it from the Pawn Shop then the computer is now his!! So can I ask the great legal minds reading this blog to comment on this statement? Is possession 9/10th of the law?

Meanwhile, how about IVF. Does it work? How well does it work? That is today’s Question of the Day from the Doctor now known as Marvin Dixon…

52. How successful is IVF?


Overall, the success rates for IVF have improved markedly since 1978 (when Louise Brown was conceived), but success rates vary widely depending on the couple’s infertility factors and the clinic performing the IVF procedure. Success rates for U.S. IVF clinics are published on the CDC’s website (http://www.cdc.gov/ART/index.htm). The standardization of clinic success rates evolved from 1994 passage of the Fertility Clinic Success Rate and Certification Act (the so-called Wyden law), which seeks to protect U.S. consumers from inflated IVF success rates. Importantly, many subtleties influence clinic-specific IVF pregnancy rates, including patient selection bias (that is, some clinics tend to treat tougher cases, so their success rates might be lower than those of clinics that take only routine cases).

For women younger than 34 years of age, most will achieve pregnancy within one to three treatment cycles; indeed, many succeed in their first attempt. For women older than 35 years, the success rates tend to decrease simply because the aging process affects the quality of these women’s eggs. For a detailed discussion of IVF success rates, couples should visit the website for the clinic where they are considering treatment. They should also discuss their specific likelihood of success with their reproductive endocrinologist. IVF pregnancy rates do vary by clinic, so patients should carefully scrutinize their chances for success at the particular clinic rendering treatment.

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Doctor Personality Issues

All doctors have different styles and as a patient I truly believe that you need to be comfortable with your physician. There is a level of trust that must exist between patient and physician and this relationship goes both ways. Some patients want to abdicate all decision making responsibility and others want to agonize over every minor point sending their RE emails several times a day.

Overall, I think that I have a pretty good rapport with my patients and thus I am puzzled by the fact that twice in as many weeks I have had patients comment to the nurses that I am the “mean” or “serious” doctor in the practice. These were Dr. D's patients and I must admit that I did not do any routines for these patients from Monty Python and the Holy Grail nor used any references from Star Wars in my interactions with them. Go figure. So for any of those patients passing through the hallowed halls of Dominion Fertility, let me know if I have somehow undergone a personality change. This has happened in the past….

During my 2nd year of residency at Stanford our first child was born and he was what is known as a “fussy baby.” Sleeping was not his thing and so when I was on call at the hospital my wife was awake all night at home. So when I got home after 36 hours on call she would hand me Seth and say “he’s all yours.” It got so bad that my fellow residents took up a petition for us to put him on rice cereal to end the madness. The medical students who had previously given me good ratings turned on me labeling me “the type of doctor that I hope never to become…”

So enough about me…back to IVF and when to use it. Here is the “Question of the Day” from the book written by your favorite mean and serious RE…

51. How do I know if I need IVF?

Not all patients need IVF or are good candidates for IVF. Thus the answer to this question can be determined only after you undergo a comprehensive infertility evaluation by your reproductive endocrinologist. Nevertheless, some situations clearly require the use of IVF. For example, women with absent or severely damaged fallopian tubes should be treated immediately with IVF. Likewise, IVF should be performed first if the male partner has very poor sperm quality. For other patients, the use of IVF may be less clear-cut, especially given that many different treatment options exist. In such cases, the doctor should discuss with the couple the pros and cons of each option, and then all parties should jointly decide on a treatment plan.

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IVF for Dummies (Part 2)

The stimulation part of the IVF cycle can be the most problematic. If patient is prescribed too little medication then she can get cancelled for a poor response. Give a patient too much and she can develop OHSS which really sucks (as was pointed out in a comment recently by one of my 5 regular readers-my Mom not included). How do we pick the protocol? Well first of all I consult my Magic 8 Ball toy that I bought on Ebay…then I spin a big wheel in my office and then I review it with Dr DiMattina, my partner, who usually changes the dose all around reminding me that he has been doing IVF since before I was in college and didn’t I read the latest paper in Fertility and Sterility. Actually, Mike and I usually agree on protocols although I really like the stop Lupron protocol for low responders and he is not a believer and uses MDL flare (which I also like…). If these comments make absolutely no sense to you, then don’t panic. If you agree or disagree with them and can cite the latest journal articles to support the thesis then you are really much too involved in your own care and are probably driving your spouse/partner over the edge.

But seriously, I review past stimulations, look at the appearance of the ovaries on sonogram and check the FSH level. From these I make my best estimate as to how to stimulate the patient. Usually we are on target. We average 11 eggs/retrieval here and that I think is ideal. Not too many…not too few..

So onto Part 2 of IVF for Dummies. Maybe I should call it something more PC but you may want to check out the book sales for those Dummies books. Not too shabby.


50. What is IVF and how is it performed?


PHASE 2: OOCYTE RETRIEVAL
Many physicians perform IVF as an office-based procedure, whereas others utilize a free-standing surgery center. Some programs are located within a hospital. There are advantages and disadvantages to each of these. We prefer to perform the egg collection within our office, as the location and staff are familiar to the patients undergoing the IVF process. We also find that the location of the IVF lab within the office encourages continuous communication between patient, physician, and embryology staff. However, clearly many successful programs utilize a surgery center or a hospital. The use of a hospital setting may allow patients with significant medical conditions (cardiac disease, severe pulmonary disease) to undergo IVF, whereas such patients would be considered an anesthesia risk in the office setting.

Although many patients are nervous about the oocyte retrieval, in fact the vast majority of women find it to be less uncomfortable than some of the screening tests leading up to IVF. The egg collection is performed under light conscious intravenous sedation using a vaginal ultrasound probe with a special needle guide adapter. The needle passes through the side of the vagina into the ovary, and the follicles are easily aspirated. The fluid containing the eggs is then inspected by the embryologist using a microscope. Both the eggs and the sperm are then placed together in small plastic dishes containing media and incubated for the next 3 to 5 days. If there is a significant male factor, then ICSI is performed several hours after the egg collection.

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IVF for Dummies (Part 1)

Clearly Reproductive Medicine changed forever after the birth of Louise Brown in 1978. The first US IVF baby did not arrive until 1980 with the birth of Elizabeth Carr. I was up on Capitol Hill a few years ago on a committee promoting insurance coverage for fertility care and Elizabeth was on the panel with me. I asked her why her Mom had remained in the hospital in Virginia for the entire pregnancy and why they had come down from Massachusetts. She explained that IVF was not available in Massachusetts at the time and may have even been illegal. Wow, how times have changed given that Massachusetts has mandated statewide fertility benefits now….But why not go home after the pregnancy was established? She told me that there were so many death threats against her parents that for their safety they stayed in the hospital under an assumed name. Hard to believe. I only rarely use an assumed name and usually it is while I am cruising websites to see how badly I am being bashed in cyberspace. Hey, in Hollywood people read their own reviews don’t they???

Over the next few blog posts let’s review IVF and discuss some hot topics. First we will start at the beginning with the basics. I will break this into 3 posts so those with short-attention spans will not be distracted like Dori in Finding Nemo. So as our book slowly rises in the Amazon.com ratings here is the Question of the Day from 100 Questions and Answers about Infertility…

50. What is IVF and how is it performed?


In vitro fertilization (IVF) was first successfully performed in Oldham, England, in 1978, resulting in the birth of Louise Brown. Since then, more than 1 million children have been born using IVF. The introduction of this technique completely changed—and greatly improved—our ability to treat even the most difficult cases of infertility, many of which were previously untreatable. Although it is clearly not a “cure-all” for infertility, IVF has revolutionized our approach to, and understanding of, the disease called infertility. IVF literally means “the fertilization of eggs with sperm in the laboratory.” An IVF cycle consists of several discrete phases, as detailed in the sections that follow.

PHASE 1: OVARIAN STIMULATION
A woman’s ovaries contain thousands of fluid-filled sacs called follicles. Inside each follicle is an egg (or ovum). In a normal reproductive cycle, only a single follicle (and egg) reaches maturity. Although Louise Brown (the world’s first IVF baby) was produced in a natural cycle from a single follicle, this form of IVF is less efficient because it often leads to cancelled cycles as a result of premature ovulation prior to the egg collection or the failure to retrieve the single egg that is produced. The introduction of injectable gonadotropin drugs enabled physicians to increase the efficiency of IVF through the production of multiple mature follicles. Two forms of these medications are used: (1) drugs containing equal parts of the pituitary hormones follicle-stimulating hormone (FSH) or luteinizing hormone (LH) [Menopur] or (2) drugs containing only FSH (Bravelle, Gonal-F, Follistim). Both kinds of medications induce the growth of multiple ovarian follicles, so it is important to monitor the woman’s response to them carefully with ultrasound and blood hormone testing.

Estrogen is produced within each of the developing follicles and induces the growth of the lining of the uterus (endometrium). Unfortunately, the rise in estrogen can also induce the pituitary gland to prematurely trigger ovulation, resulting in the cancellation of an IVF cycle. Two other classes of drugs are used to reduce the chance of this problem occurring during an IVF stimulation: (1) GnRH agonists (such as Lupron and Synarel) and (2) GnRH antagonists (such as Centrotide and Antagon) . Lupron (or Synarel) is usually started 1 week prior to the woman’s anticipated next menstrual cycle. Given that a patient may have spontaneously conceived during this cycle, all women beginning Lupron are recommended to use a barrier form of contraception. Approximately 1 week after starting Lupron, the woman should experience a normal menstrual period. An ultrasound exam is performed at the start of this menstrual cycle to examine the ovaries and measure any existing cysts. In some cases, empty follicles from a previous cycle will persist and may influence the response to FSH. If the baseline ultrasound and blood tests are normal, then the patient receives instructions that afternoon as to when and what dose of medication she should take and when she should report back to the office for repeat ultrasound and blood tests.

Patients remain on Lupron to prevent the premature release of the eggs until the end of the stimulation phase. During a typical treatment cycle, they take daily injections for 9 to 12 days before the follicles reach maturity based on their ultra- sound results and blood hormone levels. Once the follicles reach a 20- to 24-mm diameter, the woman receives a final injection of human chorionic gonadotropin (HCG; Pregnyl, Profasi) at a precise time. This hormone serves as a trigger to incite the final maturation and release of the egg (ovulation). Ovulation typically occurs about 40 hours after this shot, so the egg collection procedure is scheduled for 34–36 hours after the HCG injection.

Cycles using GnRH antagonists are somewhat different. GnRH antagonists are started several days following the start of ovarian stimulation with gonadotropins. Most clinics add the GnRH antagonist once the largest follicle reaches a diameter of 14 mm. This medication effectively prevents the release of LH from the pituitary within hours of administration. Although many clinics have used GnRH antagonists successfully as part of their IVF stimulation protocols, some studies have demonstrated a trend towards decreased implantation rates in IVF cycles using this class of medications.

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Are Babies from IVF Normal?

The astute reader of this blog may come to the conclusion that Dr Gordon is not normal. I mean the guy likes Monty Python, couldn’t get a date in high school, tells bad jokes and yet somehow managed to convince a PhD in Engineering to marry him and reproduce with him. Go figure. What really does it mean to be normal? I banged my head on the kitchen counter this morning when I saw that the Red Sox lead over the Yankees was down to 2 and a half games. Is that normal behavior? Well, for a Sox fan it is but that is besides the point.

So many questions arise when considering the normalcy of children after IVF. Are they normal? Will they get 2400 on the new SAT? Will they cheer for the Red Sox against the evil empire? Who knows. However, a lot of attention has been focused on the issue of birth defects after IVF so here is today’s Question of the Day from 100 Questions and Answers about Infertility.


53. Are the children born after IVF normal?


The question of the health of children born after advanced fertility treatments is one that has great importance both to the parents and to fertility physicians. In general, the data regarding the outcomes for children born after IVF, either with or without the use of ICSI, have been extremely reassuring. The problem with these studies remains the identification of an appropriate control group with which to compare the rate of problems found in the children conceived with advanced fertility techniques. Overall, most studies suggest a background risk of birth defects in naturally conceived children of approximately 4% to 5%. However, these couples tend to be younger than the couples undergoing IVF and, by definition, do not suffer from infertility. Although the vast majority of studies suggest no increased risk of anomalies in children conceived after IVF, none of these studies have looked at the rate of congenital anomalies in children conceived naturally but born to parents who suffered infertility that spontaneously resolved without treatment. This group of patients would clearly represent a more appropriate control group with which to compare with patients who seek out advanced fertility treatments.

One recent study from Australia (Hansen, M et al, Human Reproduction 20 (2):328-338, 2005) was a systematic review of all studies that had previously examined the possible increased risk to children conceived after treatment with IVF and/or ICSI. However, many of these studies compare the rate of congenital abnormalities in children conceived spontaneously with the rate in children who were born to older couples undergoing IVF and/or ICSI. In many studies the rate of congenital anomalies in the control group have been around 4%, whereas the rate of congenital anomalies in the group of couples undergoing IVF and ICSI have been 6% or greater. The difference between 4% and 6% is statistically significant and suggests that there may be an increased risk to children conceived through the use of advanced reproductive techniques. However, the question remains as to whether this is a problem related to IVF itself or to the underlying infertility that leads to the use of IVF. In any case, most patients accept an increased absolute risk of 2% as being reasonable, especially given that their options for spontaneous conception may be significantly limited. The greatest risk to the children conceived after fertility treatment is that of prematurity related to multiple pregnancy.

Several strategies are used to reduce the rate of multiple gestations (see Question 54, which deals with how many embryos to transfer in IVF). The risks of prematurity are significant and should not be discounted quickly, especially given that 50% of twins deliver a month or more before their due date. In addition, the question has been raised as to whether even
IVF singleton pregnancies are at higher risk for low birth weight and prematurity. If true, the cause of this increased risk may be difficult to determine.

Patients undergoing IVF suffer from infertility, so that any increased rate of adverse pregnancy outcome might not be so much a result of the IVF process as it is related to the couple’s underlying problem ofinfertility. Several studies have suggested that women who conceive spontaneously, but who have a preceding history of infertility, have a significantly increased rate of prematurity and pregnancy-related complications such as placenta previa, abruption, and low-birth-weight infants. Another way to look at the question of whether any risk is related to the process of IVF itself versus the patient who is undergoing IVF is to examine the pregnancy outcomes in women who undergo IVF and then use a gestational carrier (carriers usually have an excellent reproductive history). A study of these pregnancies found there was no increased risk of prematurity or low birth weight in the children conceived and carried in this way. This reassuring outcome would suggest that the problem lies not so much with the IVF process but, unfortunately, with the patients who require IVF to conceive.

The impact of new and emerging technologies on the rate of congenital anomalies in children born after fertility treatment remains a subject of ongoing debate. The potential risks inherent in micromanipulation of the embryo prior to embryo transfer—like that required for preimplantation genetic diagnosis (PGD)—remain unknown. Although more than 4 million IVF babies have been delivered worldwide to date, only a relatively small number of children have been delivered after the use of PGD or another emerging technology (such as egg freezing) or following unusual situations such as performing rescue ICSI on the day following egg collection because of unanticipated failed fertilization. When considering such novel treatments, the physician needs to inform the patient /couple of any known or suspected risks. Currently, several studies are under way in this country and throughout the world to continue to monitor the health of those children delivered following advanced fertility treatments.

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Sex, Drugs, Rock and Roll....

Back in high school I was the well-behaved, straight A student, Eagle Scout, nice boy who would never do drugs or drink…so of course, no girl would give me the time of day. My wife believes that the real cause of my high school social isolation was the fact that I was a science fiction fan who went to science fiction conventions and had dinner with noted authors like Hal Clement (my high school chemistry teacher), Larry Niven, Isaac Asimov to name drop a bit… She reminds me that this part of my history was kept concealed along with the Monty Python memorization issue until well after we were married. Right now my old high school (Milton Academy) has been in the news because of a sex scandal involving hockey players, a young girl and well….you can guess the rest (or check out the book now available about the whole mess: www.washingtonpost.com). Needless to say this was not my experience at Milton Academy.

So are drugs always bad? Yes, as far as my teenage son is concerned but for fertility patients drugs can be very helpful. Although we can perform IVF without medications (Natural Cycle IVF) most programs use fertility medications to increase the odds of success. The same is true for cycles of IUI (intrauterine inseminaton). Here then is today’s Question of the Day from 100 Questions and Answers about Infertility the book that contains no information about the Milton Academy sex scandal.


42. Which fertility drugs are used with IUI, and why are they used if I already have normal periods?


IUI can produce fair success rates when combined with fertility drugs. Many studies show superior pregnancy rates when IUI is combined with either Clomid or injectable gonadotropins, as compared to using these medications alone. For this reason, most infertility experts will recommend IUI to their patients when treating them with fertility drugs. In women who fail to ovulate regularly, the goal of drug therapy is to induce the growth and release of a single mature egg. This treatment is known as ovulation induction. In contrast, the treatment goal for women with regular menstrual cycles is to induce the growth of multiple follicles with the subsequent release of multiple eggs. Hence the term superovulation (also called controlled ovarian hyperstimulation) is used to describe this situation. During a cycle of superovulation and IUI, the goal is to develop 3 to 5 mature follicles, whereas the goal in an IVF cycle is 10 to 15 mature eggs. Clomid is the fertility drug of first choice for both ovulation induction and superovulation with IUI. Women who fail to respond to Clomid or who fail to conceive may be candidates for treatment with injectable fertility medications (gonadotropins) combined with IUI. In some cases, it is best to skip the treatment with Clomid and instead proceed directly with gonadotropin therapy; this decision depends on the severity of the couple’s infertility situation. In women who have normal, regular ovulation and menstrual cycles, it would appear on the surface that IUI alone without fertility drugs would be as successful as IUI with fertility drugs. Unfortunately, this simply is not the case. Instead, the combination of IUI and fertility drugs to induce superovulation yields a synergistic benefit over either treatment alone.

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Is there any hope?

We are often asked the difficult question of whether there is any hope when the beta levels are not rising appropriately. The short answer is that there is always hope and yet I wish that I could know the outcome as soon as possible so that I could spare patients that roller coster ride of emotions when things are not going according to the textbooks. However, I have become very cautious about writing off pregnancies too early. There are several patients who love to write at the bottom of their Christmas cards little reminders like “The little boy in the reindeer sweater is the pregnancy that you thought was never going to end well.”

Hey, I am only human and you can only take so much abuse from your patients before you learn to keep your mouth shut and just let it ride…

So given today’s question on the INCIID bulletin board here is the Question of the Day from 100 Questions and Answers about Infertility, the book that has not yet been featured on MSNBC unlike that other book 100 Questions and Answers about Cancer and Fertility…Oh well, that is a good book too.


80. My beta­HCG levels are as follows: 260 mIU/mL 14 days after a day­3 embryo transfer, 500 mIU/mL 16 days post transfer, 900 mIU/mL 18 days post transfer, and 1900 mIU/mL 20 days post transfer. Is there any hope for this pregnancy?

In a normal early pregnancy, regardless of the method of conception, the woman’s blood beta-HCG levels will roughly double every 48 hours. Failure of the beta-HCG levels to double suggests an abnormal intrauterine pregnancy or an ectopic pregnancy. Given that biologic variation can occur in both normal and abnormal pregnancies, however, we cannot assume that a pregnancy is in jeopardy simply because the beta-HCG levels fail to perfectly double. In the case described in the question, the woman’s beta-HCG levels did not double, but she could have either a normal intrauterine pregnancy, an abnormal intrauterine pregnancy, or an ectopic pregnancy. This determination can be made only by performing a transvaginal ultrasound examination. Even then, the results may be inconclusive. In our practice, we have seen several cases in which patients had dramatically abnormal beta-HCG levels associated with a first sonogram, suggesting an early blighted ovum pregnancy, only to discover later that the pregnancy was completely normal. Another common cause for abnormal increases in the beta- HCG level is multiple pregnancy. When patients undergo transfer of two or more embryos, a multiple gestational pregnancy may occur. In roughly 40% of these pregnancies, spontaneous fetal reduction of the extra implanted sacs occurs, resulting in a sudden drop in the beta-HCG level. Initially this decrease might be falsely interpreted as an apparent problem with the pregnancy when, in fact, one surviving embryo is completely healthy. For all these reasons, the blood beta- HCG doubling effect must be viewed as a guide, and not as absolute proof of the woman’s condition and future outcome of her pregnancy.

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You say tow-mah-tow and I say tow-may-tow

I agree that the medical profession has too many abbreviations and that it is hard to know how to act knowledgeable in front of your RE. So here are some helpful hints about how we on the other side of the desk pronounce various abbreviations:

RE (reproductive endocrinologist): are-ee
IVF (in vitro fertilization): eye-vee-eff
GIFT (gamete intrafallopian transfer): gift NOT gee-eye-eff-tea
ZIFT (zygote intrafallopian transfer): zift NOT zee-eye-eff-tea
FET (frozen embryo transfer): eff-ee-tea NOT fete
ICSI (intracytoplasmic sperm injection): ick-see NOT eye-see-ess-eye
POF (premature ovarian failure): pee-oh-eff NOT poff
PCOS (polcystic ovarian syndrome): pee-see-oh-ess NOT pee-cos
PGD (preimplantation genetic diagnosis): pee-gee-dee
ASRM (American Society of Reproductive Medicine): as-ram OR ay-ess-are-em

If there are other abbreviations that anyone needs help with just post a comment and we will discuss it.... But don't stress out just read the post below...


86. What role does stress play in causing infertility?


Not surprisingly, dealing with infertility can itself be very stressful. And stress—both physical and psychological—can significantly affect a woman’s ability to conceive. A recent study examining the role of psychological stress in successful pregnancy showed a one-third decrease in pregnancy rates in those women undergoing IVF who perceived themselves to be overly stressed. Most of these women were lawyers whose stress was perceived to be job related. Excessive physical stress can also be detrimental to a woman’s ability to conceive. Studies show that women who run more than 20 miles per week may begin to experience abnormalities in their menstrual cycle, which may in turn affect their fertility potential. Women who run marathons or compete at a very high physical level, for example, commonly have ovulatory dysfunction and infertility. There are many different ways to decrease the stress inherently present with infertility and its treatment—for example, decreasing work hours or changing jobs, exercise, meditation, yoga, acupuncture, getting a new hobby, or simply setting aside some time for oneself. Many patients are able to reduce their infertility-related stress by simply becoming more knowledgeable about the subject of infertility. In addition to providing physician counseling, we ask our own patients to read and become more educated about their infertility, thereby empowering them to take control of it. Excellent and reliable information is available at the American Society of Reproductive Medicine website (www.ASRM.org).

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Labor Day at Dominion

Labor Day is not a real funny holiday for fertility patients. It is really an obstetrical holiday and having worked a fair number of Labor Days during my residency everyone thought that it was so clever to quip about being in labor on Labor Day…yup, a real yuck fest.

Of course, for REs the funny holiday is Easter. Not for the religious significance but of course, for all the Easter egg jokes. Same phenomenon of really bad jokes occurs as patients who undergo egg collection on Easter are participating in an “egg hunt” of sorts.

Hey, I don’t make this stuff up, I just pass it on..you know, life is not like an episode of Scrubs.

So back to our introductory questions on infertility. Clearly infertility is a common disorder as you can read below. In the Gordon household we did not deal with infertility per se, but had the emotional distress of dealing with recurrent pregnancy loss instead. My 16 year old son Seth wished we had infertility. When we announced that we were pregnant, Seth looked at me and asked quite seriously: “Dad, how did this happen?” I replied “What do you mean?” Seth, at that time age 12, fired back “I mean did you take Mom to your office or what?” “No," I replied, "this was the old-fashioned way.” And that was way too much information and Seth wanted to hear not another word on the subject of his parents procreative activity.

Without further ado, here is the Question of the Day:


3. How common is infertility?


Infertility is an extraordinarily common disorder. An estimated 25% of all women will experience an episode of infertility during their lifetime. Infertility currently affects about 6.1 million women and their partners in the United States. The percentage of reproductive-age women who report problems successfully conceiving and delivering a pregnancy varies with age. In the youngest segment of the population, approximately 10% to 15% are affected by this problem. Among women older than age 35, however, more than one-third report diminished fertility. The rates of pregnancy loss are also related to a woman’s age, with the rate of miscarriage exceeding 50% in women older than age 40.

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Back to Basics

Ah, the end of summer. How sad that always made me as a little kid. It meant loading up our station wagon and driving back from Cape Cod after spending the whole summer in West Dennis. It meant no more mini-golf and no more trips to the beach and of course, the beginning of a new school year. Fall was not a favorite of mine as it meant classes and homework and the approach of winter. But times change and now I relish the change in the weather, especially here in DC where August is so hot and humid (pretty much like June and July!). And since I am no longer in school the feeling of dread in the pit of my stomach is not a problem…

So what does this have to do with infertility? Nothing. Well, almost nothing. I just think that with the beginning of a new academic year upon us we should step back and address some basics since we had covered some pretty specific issues in reproductive medicine. So here we go with some of the basic questions from 100 Questions and Answers about Infertility…


2. What is infertility?

Approximately 80% to 85% of couples who are trying to become pregnant will successfully conceive within a year. Thus infertility is commonly defined as the inability to achieve a pregnancy within 12 months of unprotected intercourse. However, certain patients may have recognized factors that would lead to problems conceiving; for them, the 12-month period of waiting would make no sense. Common examples of such women include those who have extremely irregular periods, a history of severe endometriosis, a history of previous tubal pregnancies, or other anatomical factors that would clearly lead to diminished fertility. Such couples are encouraged to seek evaluation for infertility if the woman is older than age 35 and they have been attempting pregnancy for a total of 6 months without success. Another problem related to reproduction is recurrent pregnancy loss. Many women can readily conceive, only to suffer repeated pregnancy losses. These women represent a special subset of those who are unable to successfully reproduce and should be evaluated by a medical professional.

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What's the Plan?

Patients can usually be divided into active and passive subtypes. Active patients read books (like this one), cruise the internet, pepper their RE with questions and engage in extensive discussions of the options available to them. Passive patients look across the desk at us and say “Doctor, you decide what is best.” Although at the end of the day, the active patients can certainly leave you feeling exhausted, I really enjoy these interactions and the challenge of making a treatment plan with them. I worry about the passive patients. Do they really understand what they are doing? Can they justify the treatments that they are pursuing in terms of finances and the emotional/physical/psychological costs of infertility care? If they abdicate all responsibility for the decision making process then I am left on the hot seat.

So when making a plan where do we start? First of all, we consult the “Magic 8 Ball” of fertility care and whatever treatment appears in that little window is what we do…not really. This question is the “Question of the Day” from the book that has yet to generate any interest in Hollywood…although rumor has it that Matt Lauer wants to play me if the movie ever gets made.

18. How will my reproductive endocrinologist determine a plan of therapy?

In general, reproductive endocrinologists recommend a particular course of treatment only after obtaining the results from the full spectrum of fertility tests. These tests usually include a pelvic ultrasound, an assessment of tubal patency (hysterosalpingogram or laparoscopy), a semen analysis, and a variety of blood tests. The therapeutic plan for any couple is unique to them. If testing has demonstrated a clear problem, such as blocked fallopian tubes or a markedly abnormal sperm count, then in vitro fertilization (IVF) may be recommended as the only reasonable alternative.

However, most couples are not sterile but merely subfertile, so they may be offered a range of therapeutic options—from expectant management, to the use of insemination with or without fertility drugs, to IVF with or without intracytoplasmic sperm injection (ICSI). IVF can be performed using the patient’s own eggs, donor eggs, or donor sperm. A couple’s particular therapeutic plan will be developed with their specific needs in mind. For those patients in whom IVF is not an option, whether because of religious, financial, or philosophical reasons, the physician will offer counseling about the alternative treatments available to them. Not all couples are prepared to undergo extensive treatments for their infertility, so their physician will likely tailor the options appropriately when proposing a course of action to a particular couple. Given that infertile couples can sometimes achieve spontaneous pregnancies, the desire of a couple to proceed with therapy needs to be weighed against the likelihood of success for that therapy and the cost involved. These costs may include financial, physical, and emotional considerations.

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Going to Blast! Part 2.

So yesterday we discussed blastocyst transfer in general and today we get down to brass tacks…You know, it amazes me that some of the Residents and Medical Students that I teach do not know some of these quaint little sayings like the one I just used. I have said to them “a watched pot never boils” and received just blank stares. Is this a sign of advancing age on my part or is it because they watched too much TV as kids? I have no idea. All I know is that it still really disturbs me that the 80s music that I listen to in the operating room was released before some of the medical students were born! Yikes.

In any case, back to blast transfer. So how do we choose? That is the “Question of the Day.” So if you are wracked with guilt over reading these questions for free rather than buying the book 100 Questions and Answers about Infertility, then ease your guilty conscience and click over to Amazon.com pronto!



70. My clinic allows me to choose between a day­3 and a day­5 embryo transfer. How do I
decide?

The decision to transfer embryos on day 3 or day 5 is one that requires careful thought. In general, embryos that have formed blastocysts have a better chance of implanting successfully. Unfortunately, not all embryos will progress to the blastocyst stage outside of the body. This inconsistency raises the question as to whether the embryos that fail to form a blastocyst would have initiated pregnancy had they been transferred back into the uterus on day 3. Some studies have, indeed, demonstrated acceptable pregnancy rates with day-3 transfers of embryos that were of marginal quality and that, based on historical data, would have been unlikely to form blastocysts in culture. Clearly, the pregnancy rate in the absence of an embryo transfer will be zero, whereas even embryos of borderline quality, if transferred on day 3, may potentially lead to a pregnancy.

So how can you decide between a day-3 and a day-5 embryo transfer? Many clinics make the decision on day 3. If a patient has a certain number of high-quality embryos on day 3, then the embryos are maintained in culture for 2 additional days to allow for further embryo selection at the time of transfer. If the embryos fail to progress to the blastocyst stage, however, then there is no transfer—which often results in profound patient disappointment. If a limited number of embryos are available on day 3 and no embryo selection is needed, then the benefit of a day-5 embryo transfer may be limited.

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Going to Blast!

“Going to blast” is different than “having a blast.” When your RE talks about going to blast he/she is referring to the stage of embryo development at the time of the embryo transfer. When I began practicing infertility in 1996 most embryo transfers were done on the second day after egg collection (egg collection is day zero). However, most clinics moved rapidly to day 3 ET to allow for better embryo selection. The move to day 5 ET was a bit more difficult as commercially available media was a problem and by media I am not referring to CD or DVD but to the liquid that embryos are cultured in after retrieval of the eggs. Now many clinics have had very good success with day 5 ET and it has become more common. So today’s question is the simple one whereas tomorrow we will deal with the pro/cons of blast transfer. Of course, if you are dying to hear the next question you can always run down to your corner bookstore and purchase “100 Questions and Answers about Infertility.” There are a couple of copies left at the Barnes and Noble at Clarendon (Arlington, VA)…I know because I put them on the shelf (actually, I didn’t but I admit that the thought crossed my mind).

69. What is a blastocyst transfer?

Embryos on the third day after egg collection are referred to as cleavage-stage embryos. At this point, each embryo contains 6 to 10 discreet cells (blastomeres). When assessing these embryos for quality, the embryologist grades them based on the number and appearance of the blastomeres. Embryos that have equal-size blastomeres with no fragmentation are usually given a high grade, whereas embryos that have extensive fragmentation with unequal-size blastomeres are given a low grade. In general, higher-grade embryos have a much better chance of implanting successfully and generating a pregnancy. If the embryos are maintained in culture beyond day 3, they first form a solid ball containing approximately 30 to 50 cells, called a morula. Over the next day or two, this solid ball of cells becomes a hollow sphere with a clearly defined inner cell mass. This hollow ball of cells is called a blastocyst. Many clinics maintain the embryos in culture until the fifth day to allow for improved selection of embryos to transfer. Patients who undergo an embryo transfer on day 5 or 6 after egg collection are referred to as having a blastocyst transfer.

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Why is nothing working?

Clearly the million dollar question that all patients usually ask is "why is it not working?" The "it" can range from natural attempts at conception up to and including IVF. In some cases we really don't understand what the problem is and are faced with approaching fertility treatment with the "more eggs, more sperm...in the right place at the right time" approach. This logic is really the basis of most of our treatments. However, paradoxically we often recommend the most expensive and invasive treatment to those without an identifiable problem..why? Are we just a bunch of greedy, money grubbing slime bags?? Yes....no wait that describes only a few of us (just kidding, I hope). So why the aggressive approach in these cases? Well, here's the problem. If a couple fails to conceive on their own or after an IUI we have learned nothing new.

Did the egg ovulate? Unknown.
Did the tube catch the egg? Unknown.
Did the sperm find the egg? Unkown.
Did the sperm fertilize the egg? Unknown.
Did the egg divide? Unknown.
and so on...

At least with IVF we can provide some answers to the above questions.

So that leads to today's Question of the Day....and for all those who read this blog (besides my Mother) and have copies of the book, how about some 5 star reviews on Amazon.com? You don't usually have to beg for reviews but hey, I need that $0.27 per book to pay for my new laptop. So here is today's question:

68. Why would my doctor suggest IVF if all of my tests are normal?

Upon completion of the diagnostic evaluation, approximately 10% to 15% of couples will be found to have unexplained infertility, meaning that all of their tests are normal. Such couples are probably best called “subfertile,” and most can successfully conceive with IVF. Prior to the introduction of IVF, couples with unexplained infertility had a poor chance of achieving pregnancy with other treatment methods. We do not know precisely why couples with unexplained infertility are infertile. Some evidence suggests that the source of the problem may be tubal dysfunction or sperm egg interaction. Often, an infertility center uses IVF together with ICSI in such couples to ensure that fertilization of the ova occurs. Thanks to these techniques, today couples with unexplained infertility have a very strong likelihood of ultimately achieving a successful pregnancy with IVF.

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How to do an FET

In my last blog post I discussed the general concept of frozen embryos which is certainly a bit of a mind bending concept by itself. But I want to emphasize how important the option of having cryopreserved embryos can be to a patient’s overall chances for success. Many times over the years we have ended up with success by using the last frozen embryo that a patient had to work with after multiple failed cycles. Of course, the natural response would be that if we were really smart, then we should have known which embryo out of the whole bunch would go on to make a baby. I agree, but we are not that smart…yet. So until that time we all just have to ride that emotional roller coaster up and down as we try our best to achieve success.

As we head into one of the final weekends of summer let’s discuss the process of setting up an FET and review how do we get those frozen embryos back inside of our patients at the right time in the reproductive cycle. Here is today’s “Question of the Day” from 100 Questions and Answers about Infertility: the book that so many people are having trouble putting down because we coated the outside with superglue.

76. What is the difference between a natural­cycle frozen embryo transfer (FET) and a medicated FET?

There are two possible options for performing a frozen embryo transfer (FET): natural-cycle FET and medicated FET. Natural-cycle FET is available to women with regular ovulation and monthly menstrual cycles. In patients with predictable menstrual cycles, we can carefully monitor the cycle to determine the precise timing of ovulation. Alternatively, ovulation can be induced with the administration of an HCG injection. Once the precise date of ovulation is set, then the uterine lining should be receptive to embryo transfer 5 days later (for embryos frozen on day 3 in a previous IVF cycle). In this way, the embryos can be replaced at approximately the time when they would normally be arriving in the uterus.

One problem with natural-cycle FET is that the optimal time for implantation may fall at an unpredictable time during the laboratory work schedule. In addition, natural-cycle FET demands frequent patient monitoring around the time of ovulation. If a cycle is suboptimal in terms of the estrogen level and endometrial development, then the embryos should not be thawed and the cycle should be canceled.

A medicated FET allows the couple to avoid some of the pitfalls associated with a natural-cycle FET. In this type of FET, estrogen pills, shots, or patches are used to prepare the endometrium for embryo implantation. Three days prior to embryo transfer, the woman begins taking progesterone to modify the endometrial lining so that it will be receptive when the embryos are placed. Some clinics prescribe GnRH agonists (such as Lupron) to their female patients the month prior to a medicated FET cycle so as to reduce the chances of spontaneous ovulation. The use of Lupron reduces the chances of cycle cancellation owing to unexpected ovulation to near zero.

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To Freeze or Not to Freeze...

The previous post discussed egg freezing which is a much more difficult technique compared with embryo freezing which has a much longer, proven track-record. We will discuss egg freezing some other time. In general, if there are high quality embryos that are not going to be transferred it is always a good idea to consider freezing them for future use. However, the mere fact that these embryos exist has led to other concerns that are not only medical but social, philosophical, ethical, and moral. What obligations do a couple have to their frozen embryos? Several years ago over 4000 frozen embryos were destroyed in England because the couples who had created them had abandoned them and the clinics had no other option given that the status of these embryos was uncertain.

In this country several high-profile law suits have grown out of disputes following divorce of who controlled the embryos. Similarly a clinic in New England was sued by a man whose ex-wife had undergone a frozen embryo transfer following their divorce without informing the clinic of her change in marital status. In this case the clinic ended up paying a pretty hefty settlement as the man argued that his decision to NOT reproduce should have trumped her decision to reproduce with embryos that were from his sperm...yikes.

http://www.ivf.net/ivf/index.php?page=out&id=263
http://www.boston.com/news/science/articles/2005/05/18/technology_legal_gaps_leave_embryos_in_limbo/
http://www.all.org/abac/efd001.htm

So although I am all in favor of freezing these extra embryos one must proceed with caution. If you are still with me then read on as we cover today's Question of the Day from 100 Questions and Answers about Infertility: the book that still needs all (?some) of you to write some reviews on Amazon.com as they keep rejecting the ones that my mother has sent in..


75. What is embryo freezing, and how successful is it?


On the day of embryo transfer, the couple may learn that they have additional embryos of good quality in addition to those embryos that have been selected for embryo transfer. These embryos can be cryopreserved by freezing them in liquid nitrogen. Through a series of carefully orchestrated steps, the embryos are ultimately frozen at a temperature of –196 °C, leaving them in a state of suspended animation in which they can remain for many years. Embryos that have been stored for more than 10 years have successfully generated pregnancies (although most patients tend to use their frozen embryos within 3 to 5 years after they are produced). The pregnancy rates associated with replacing frozen embryos depend on the age of the patient and the quality of the embryos at the time of cryopreservation. Top-quality embryos from young patients may yield pregnancy rates around 50%, whereas poor-quality embryos may not even survive the thawing process. In some clinics, more than 75% of embryos survive the freeze–thaw cycle. Many couples are often concerned about their moral obligations concerning their frozen embryos. In such cases, couples may elect to defer embryo freezing, choose to alter their stimulation or pursue natural cycle IVF so as to avoid this problem of excess embryos. Extra embryos that are not used to initiate a pregnancy could represent a source of embryonic stem cells. This potential use of extra embryos lies at the heart of the recent political debate in the United States regarding government funding of stem cell research. Clearly, patients should carefully consider the implications of excess frozen embryos as they embark on an IVF cycle. However, not all patients will have extra embryos of high enough quality to be considered for embryo cryopreservation.

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Cross Generational Egg Donation and Beyond

A recent case in Canada raises some very interesting ethical questions. A women with a young daughter with Turner Syndrome wished to undergo IVF with cryopreservation of the unfertilized eggs so that her daughter could use them later in her life in order to conceive rather than rely on another egg donor to provide her this opportunity for parenting.

http://www.associatedcontent.com/article/221699/medical_first_mother_to_daughter_egg.html

Never a dull moment in the world of reproductive medicine! In the above situation the girl would give birth to her 1/2 sister and raise her as her daughter. Well, I must admit that is a new one on me although I have been asked whether we could use a patient's daughter from her first marriage as an egg donor for her and her new partner. In this case, the patient's ex-husband would be the genetic grandfather of the child born to her and her new partner. Try that question out on the cocktail party circuit.

So would we do the daughter to mother egg donation? We elected not to...as the issue of consent was problematic given the unmeasurable issue of coercion between parent and child. We used to discuss such cases at UCSF with Dr. Mary Martin who served on the Ethics Committee of the American Society of Reproductive Medicine. Dr. Martin described such cases as having a high "yuck factor." The "yuck factor" was that intangible aspect of a case that simply causes a visceral negative reaction.

So what about screening tests for egg donors (and their recipients)? That is the topic of today's question of the day from 100 Questions and Answers about Infertility, the book that has yet to crack the 500,000 mark on Amazon.com.

84. What screening tests are performed on donors?


Both the ASRM and the FDA have issued clear screening guidelines and regulations for egg and sperm donors; the guidelines are available on these organizations’ respective websites. A typical evaluation involves a comprehensive history of the donor’s health and his or her family. A physical examination and comprehensive laboratory screening tests for communicable diseases are also performed. Many centers add genetic testing of the donors. A psychological assessment of all ova donors is routinely performed. Although the anonymous donor’s anonymity is preserved, the results of his or her laboratory tests, psychological profile, physical characteristics, and historical information are shared with the infertile couple. This information allows couples to carefully choose their donor and provides a certain level of comfort in knowing that proper screening was performed. Some clinics provide adult photos of their donors, but in our practice we have limited photos to those from childhood to preserve the donors’ anonymity

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How to Choose a Fertility Clinic

Not a week goes by when a couple asks during a consultation "Why should we come here instead of clinic X." I know that many fertility books advise patients to ask this question but what response are they looking for....

This question always takes me back to my college, medical school and internship/residency interviews and to tell the truth I usually interviewed badly. My Harvard undergrad interview was particularly memorably bad and I remember my high school guidance counselor shaking his head slowly and asking what happened. I blew it. In retrospect it was the best thing that ever happened to me at that point because I ended up at another school which is pretty well known located in Princeton, NJ. Then after a wonderful 4 years at Princeton I found myself back at Harvard for a medical school interview and I screwed up again. Meanwhile I had great interviews at Duke, Michigan and Rochester. Again fate steered me, this time south to Durham and if that hadn't happened I would not have met my lovely wife the first week of classes (introduced by my classmate, her next door neighbor). Years later I was actually really sought after to do my Fellowship in REI at Harvard but we elected to stay on the Left Coast and I went up the road from Stanford to UCSF.

So....when a patient's husband leans forward over my desk and says "OK, so why should we come here" it seems like old times. Many glib answers rise to the surface:

- because I am such a great guy.
- because I am an Eagle Scout.
- because I am such a sensitive guy and like rainy days and walks on the beach.
- because I can recite the entire script of Monty Python and the Holy Grail.
- because I am God's gift to reproductive medicine.

...and on and on.

But seriously, I never know what to say. How do you inspire confidence and yet not come out as an arrogant SOB? How do you appear to be a nice, compassionate, caring doctor and yet not get labeled as "not aggressive enough." Who knows? Not me, that's for sure.

So with that intro here is today's Question of the Day from the book that the B&N at Clarendon down the street says is coming this fall to their shelves. Just remember that this is advice from the idiot who left his laptop overnight in an unlocked car.....


7. How do I choose a fertility clinic?

Choosing a fertility doctor for your care may be the single most important factor that leads to a successful pregnancy, so choose carefully.

Many patients are referred to us by their OB/GYN, friends, relatives, former patients, news articles, or through the Internet. But the one common denominator we have routinely observed with the sophisticated patient is that she is well prepared before coming for her initial office visit or she quickly becomes informed and knowledgeable before we begin any treatments.

Patients often say to us, “I checked you out before making this appointment.” Of course, we are always flattered by such comments, but we know that this patient will ask all of the important questions and make an intelligent decision regarding her treatment options. She will also probably experience less stress during the evaluation and treatment process, as she has developed a better knowledge base and understanding of what to expect.

All fertility clinics come with a unique flavor of their own. Some clinics are run by a solo practitioner, others by 2 to 6 member groups, while others are “mega” clinics with over 15 doctors. Regardless of the size of the group, be sure you are getting the attention and treatments you desire and deserve. You should never feel like a number with a revolving door of doctors. Of course, patients are not doctors and will not have the knowledge or experience of a reproductive endocrinologist, but a caring doctor will always welcome any and all questions and will take the time to answer them in a way that you can understand. We view patients as our partners, and once we understand what they are willing or not willing to do, we can devise a treatment plan that offers hope without subjecting them to any unnecessary additional stress.

Other things to consider:

Statistics, statistics, statistics: You want a baby, so choose a fertility clinic with good success rates. However, a wise man once said: “There are lies, damn lies and statistics” So how does one determine what to make of these statistics? In truth, there is no easy answer. Clinics that are more selective can inflate their success rates while those that have a different philosophy may suffer the consequences eventhough they have an excellent program. When considering a clinic it is important to know what your specific chances for success will be within that clinic. If there is one yardstick to compare clinics, then that is the pregnancy rate using donor eggs. In this patient population the pregnancy rates should be very high. A low donor egg pregnancy rate may be concerning. Individuals should evaluate the clinic statistics and obtain a good understanding and feel for what their specific chances for pregnancy will be per treatment. Patients may also evaluate the clinic success by reviewing IVF statistics at the Centers for Disease Control and Prevention (www.cdc.gov).

Experience: Experience of the clinic, in our opinion, may be one of the most important factors when deciding which doctor and which clinic to seek for fertility care. One should ask how long the doctors have been performing various treatments and whether cutting-edge procedures are either being offered or are being developed in the practice.

Subspecialty board certification: Most doctors practicing in the field of in vitro fertilization and infertility are subspecialty board certified in reproductive endocrinology and infertility. This certification can be found by going to the Society of Reproductive Endocrinology’s Web site, which lists doctors who are subspecialty certified in reproductive endocrinology and infertility. Additionally, patients may find it beneficial to see that their doctor has a faculty position at one of the local medical universities or actively participates in the teaching of the medical students and residents in their locality.


Availability and accessibility of doctors: It is important that you have access to your doctor in order to have your questions answered and needs addressed. Evaluate whether or not the availability and accessibility of the doctor is an easy process or a difficult one when making decisions as to where to seek care. The friendliness and helpfulness of the staff will also give you a feel for the character of the practice.

Cost: It is always important to get the total cost. Factor in extra expenses such as the fertility drugs, which can cost thousands of dollars; ICSI; assistedembryo hatching; embryo cryopreservation; and preimplantation genetic diagnosis (PGD). These drugs and procedures can quickly increase the overall cost for treatment.

Finally, he is a word of caution. In general, Internet chat rooms may be a dangerous place for seeking advice regarding finding an infertility doctor. Be careful what you hear online, as it always represents just one half of the story. It is far better for you to do your own homework and research than to rely on information provided from others, which may be based on misimpressions or experiences.

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Where has Dr. Gordon been??

I know that the 5 people who read this blog have been wondering that for the past 2 weeks. Gee, he was so good about posting questions from that fantastic book and then...POOF..he disapparated. Well, the answer is that I have been here but too overwhelmed to post to the blog. Sorry but true. When returning from vacation you always get hit hard and this month was no exception. So my patients in cyberspace had to take a back seat to the real flesh and blood patients.

And then last Friday night disaster struck...Upon returning from dropping off the babysitter at midnight I made several fateful decisions....I left my laptop case in my car...I left the car open....you can guess where this is going....YUP, next morning my MacBook Pro was in the hands of persons unknown. No patient info was on the laptop but there were over 6000 photos and my iTunes (all 80s hits by the way) and all my email.

But wait...on Wednesday night I had done a complete backup of my Home folder and so after a visit to the Mac store my laptop was back but in a new body..who says reincarnation doesnt exist... However, it did still take some time to get everything loaded back and I am still not there yet.

So, dear reader, please bear with me. I will say that this whole experience has proven to me the benefit of a good backup plan!

Given my state of exhaustion let's tackle a simple little question from the book that I am trying to get into your local Barnes and Noble store: 100 Questions and Answers about Infertility. Now, I used to be pretty good about working out on the elliptical trainer but then I got plantar fasciitis and my orthotics gave me a Morton's neuroma so I have been a slug this summer.

87. Can I exercise? How much is okay?

Mild to moderate exercise is beneficial to infertility patients and is highly encouraged. Healthy amounts of exercise decrease stress and clearly improve a person’s sense of well-being. Studies show that women who exercise before and during their pregnancy have better obstetrical outcomes and healthier babies than women who are sedentary. For most patients, we recommend exercising 30 minutes per day, 4 or 5 times per week, but lesser amounts of exercise are still beneficial. Even 15 minutes of exercise each day can help reduce stress and improve your physical health. We highly recommend that women begin or continue exercising during their infertility evaluation and treatments, and perhaps more so for those undergoing treatment with IVF. In our experience, these patients are better able to tolerate the stress related to infertility and IVF.

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