Question 51. How can you have an ectopic pregnancy after IVF?

Where does the time go? Here we are the last day of May and there are so many projects that I need to get to before June.....not looking so good here at 9:35 pm. Oh well, tomorrow is another day and I will just have to keep plugging away. Currently, DrD and I are working on several papers simultaneously including a chapter on Natural Cycle IVF for a textbook on infertility. I spent hours this past weekend slogging through paper after paper trying to extract the salient information as we reviewed the experiences with Natural Cycle IVF from clinics around the world (England, Japan, Slovenia, The Netherlands, Norway.....). All those places to visit and here I am unable to get away to New Jersey for the day because I am too busy. Traveling can be tough on anyone. But an embryo that travels out of the uterus following an embryo transfer after IVF can be heart-breaking. Although many patients are emotionally prepared for IVF to fail or for them to possibly suffer a miscarriage, the possibility of ectopic/tubal pregnancy is usually not on the radar screen.

Unfortunately, ectopics can occur following IVF (albeit rarely ~ 1-3%) in spite of all of our best efforts to place the embryo precisely in the uterus under ultrasound. Still it is a real disappointing end to a treatment cycle. Most ectopics can be treated medically with methotrexate but surgery still has a role in the management of ectopics. Years ago, before electricity, when I was a resident in Ob Gyn there was a saying passed down to junior house officers...."Never let the sun set on an ectopic." In other words, get that patient to the operating room now and don't mess around.

Seems a bit dated but not unreasonable advice in some cases....

So as we move to June here is today's Question of the Day...


51. How can you have an ectopic pregnancy after IVF?


The exact mechanism responsible for an ectopic pregnancy following an IVF procedure is unknown. Some believe that embryo migration up into the fallopian tubes occurs because of local cellular activity or fluid mechanics present inside the uterus. Sometimes the opening of the fallopian tube in the uterus is dilated because of disease, making it easier for the embryos to enter the tubes.

As described in Part 3, an ectopic pregnancy can occur within the section of the fallopian tube that passes through the muscle of the uterus or within the short segment of fallopian tube that remains after surgical removal of the tube. The incidence of ectopic pregnancy following IVF ranges from 0.5 % to 3%, but this figure may be decreasing. For the past several years, embryo transfer has been routinely performed using ultrasound to properly guide the embryo catheter to the optimal uterine location, which may help to reduce the risk of an ectopic pregnancy. However, even ultrasound guided embryo transfer cannot eliminate the possibility of an ectopic pregnancy after IVF.

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Question 50. How do I decide how many embryos to transfer?

Well, we are halfway done with the 2nd Edition of 100 Questions and Answers about Infertility. I am still waiting for my invitation to go on Oprah and the book is not on the NY Times bestseller list. I am thinking about having Audible produce an audiobook version but my attorney has warned me that I could be legally responsible for those listeners that nod off while playing the book in the car and then end up off the road in a car wreck. Oh well. Guess I will need to keep coming to work.

Deciding how many embryos to transfer is not an easy decision and raises many questions. Some patients are not comfortable with the concept of embryo freezing and thus elect to transfer all viable embryos. Obviously, the RE needs to be aware of this plan and such patients may need to restrict how many eggs are fertilized in order to avoid becoming the next Jon and Kate plus Eight.... Usually, 50-75% of the eggs will fertilize and half of these will develop into embryos that are good enough to transfer or to freeze BUT this is not always the case....I have seen 6 good embryos from 6 eggs and 2 good embryos from 23 eggs...go figure.

So how can we make educated decisions about the number to transfer? Well that is the Question of the Day!

50. 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 although this attitude may be changing slowly.

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 49, 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.”

In the U.S., there is no question that the trend is to transfer of a single embryo in most patients. We fully embrace this concept. In fact, with the recent advances in embryo cryopreservation, such as vitrification our frozen-thawed embryos seem to be as likely to implant and produce a healthy pregnancy as embryos transferred in a fresh cycle. This, in the patients classified as “Most favorable prognosis” we see no need to transfer more than a single embryo and risk a multiple pregnancy when we can safely perform a frozen-thawed embryo using high-quality vitrified embryos. However, convincing patients has proved more difficult. One of the advantages of Natural Cycle IVF is that there is rarely the option to transfer more than a single embryo since nearly all patients produce only a single mature egg in a typical reproductive cycle. Some patients who had planned to undergo single embryo transfer will change their mind at the last minute and elect to transfer 2 embryos greatly increasing the risk of a twin pregnancy. With Natural Cycle IVF the temptation to transfer two embryos has been eliminated entirely.

The ASRM has published guidelines for making the decision of how many embryos to transfer (see Table 1). 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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Question 49. Are the children born after IVF normal?

The goal of all of our patients is to have a normal, healthy child. However, there are risks in life that none of us can eliminate and unfortunately any child can be born with a birth defect. So the real question is whether IVF derived pregnancies result in more complications and birth defects than non-IVF pregnancies. But here's the problem...patients who undergo IVF have a problem....INFERTILITY.

So really what we need to compare are the outcomes of pregnancies in infertile couples that conceived on their own and those that conceived with IVF...otherwise we are truly comparing apples and oranges. One very revealing study looked at pregnancies in gestational carriers (who have proven fertility which is why they were chosen to be gestational carriers in the first place!) and compared these to IVF pregnancies where patients carried themselves. Guess what? All the issues of bleeding, prematurity, low birth weight etc completely went away! So since most infertile patients do not use a gestational carrier, we need to realize that there may not be an easy way to separate out the cause and effect in terms of outcomes as the issue may be related to the patient needing infertility treatment and not necessarily the treatment itself. Twins are the clear exception as twins (at least non-identical twins) can be prevented by sticking with single embryo transfer.

I am proud to report that we have the highest percentage of single embryo transfers in the country. I know that this is true because we perform so much Natural Cycle IVF and 99% of these cycles result in only a single egg and therefore only a single embryo available for transfer.

So after that introduction, let's look at today's Question of the Day. I have included supplemental information that is in the stimulated cycle IVF consent form that we use here at Dominion. This consent form was produced by SART and provided to all US fertility clinics.

Question 49. 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 patients and fertility physicians alike. 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 is 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, few 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 clearly represents a more appropriate control group with which to compare with patients who seek out advanced fertility treatments. The few studies that have looked at this question have noted that although patients who suffered from infertility have a higher rate of anomalies and pregnancy related complications, the means by which these couples eventually conceived (spontaneously or with IVF) did not influence the rate of these problems. Therefore it may not be the IVF process per se that is the issue here but rather the underlying infertility that matters.

The following is from the SART stimulated cycle IVF consent form.....

1. Overall risks.

Since the first birth of an IVF baby in 1978, more than 4 million children have been born worldwide following IVF treatments. Numerous studies have been conducted to assess the overall health of IVF children and the majority of studies on the safety of IVF have been reassuring. As more time has passed and the dataset has enlarged, some studies have raised doubts about the equivalence of risks for IVF babies as compared to naturally conceived babies.

A major problem in interpreting the data arises from the fact that comparing a group of infertile couples to a group of normally fertile couples is not the proper comparison to make if one wants to assess the risk that IVF technology engenders. Infertile couples, by definition, do not have normal reproductive function and might be expected to have babies with more abnormalities than a group of normally fertile couples. This said, even if the studies suggesting an increased risk to babies born after IVF prove to be true, the absolute risk of any abnormal outcome appears to be small. Singletons conceived with IVF tend to be born slightly earlier than naturally conceived babies (39.1 weeks as compared to 39.5 weeks). IVF twins are not born earlier or later than naturally conceived twins. The risk of a singleton IVF conceived baby being born with a birth weight under 5 pounds nine ounces (2500 grams) is 12.5% vs. 7% in naturally conceived singletons.

2. Birth Defects.

The risk of birth defects in the normal population is 2-3 %. In IVF babies the birth defect rate may be 2.6-3.9%. The difference is seen predominately in singleton males. Studies to date have not been large enough to prove a link between IVF treatment and specific types of birth defects.

Imprinting Disorders. These are rare disorders having to do with whether a maternal or paternal gene is inappropriately expressed. In two studies approximately 4% of children with the imprinting disorder called Beckwith-Weidemann Syndrome were born after IVF, which is more than expected. A large Danish study however found no increased risk of imprinting disorders in children conceived with the assistance of IVF. Since the incidence of this syndrome in the general population is 1/15,000, even if there is a 2 to 5-fold increase to 2-5/15,000, this absolute risk is very low.

Childhood cancers. Most studies have not reported an increased risk with the exception of retinoblastoma: In one study in the Netherlands, five cases were reported after IVF treatment which is 5 to 7 times more than expected.

Infant Development. In general, studies of long-term developmental outcomes have been reassuring so far; most children are doing well. However, these studies are difficult to do and suffer from limitations. A more recent study with better methodology reports an increased risk of cerebral palsy (3.7 fold) and developmental delay (4 fold), but most of this stemmed from the prematurity and low birth weight that was a consequence of multiple pregnancy.

Potential Risks in Singleton IVF Pregnancies




In this table, the Absolute risk is the percent of IVF Pregnancies in which the risk occurred. The Relative Risk is the risk in IVF versus the risk in non-IVF pregnancies; for example, a relative risk of 2.0 indicates that twice as many IVF pregnancies experience this risk as compared to non-IVF pregnancies. The numbers in parentheses (called the “Confidence Interval”) indicate the range in which the actual Relative Risk lies.

3. Risks of a Multiple Pregnancy

The most important maternal complications associated with multiple gestation are preterm labor and delivery, pre-eclampsia, and gestational diabetes (see prior section on Risks to Woman). Others include gall bladder problems, skin problems, excess weight gain, anemia, excessive nausea and vomiting, and exacerbation of pregnancy-associated gastrointestinal symptoms including reflux and constipation. Chronic back pain, intermittent heartburn, postpartum laxity of the abdominal wall, and umbilical hernias also can occur. Triplets and above increase the risk to the mother of more significant complications including post-partum hemorrhage and transfusion.

Prematurity accounts for most of the excess perinatal morbidity and mortality associated with multiple gestations. Moreover, IVF pregnancies are associated with an increased risk of prematurity, independent of maternal age and fetal numbers. Fetal growth problems and discordant growth among the fetuses also result in perinatal morbidity and mortality. Multifetal pregnancy reduction (where one or more fetuses are selectively terminated) reduces, but does not eliminate, the risk of these complications.

Fetal death rates for singleton, twin, and triplet pregnancies are 4.3 per 1,000, 15.5 per 1,000, and 21 per 1,000, respectively. The death of one or more fetuses in a multiple gestation (vanishing twin) is more common in the first trimester and may be observed in up to 25% of pregnancies after IVF. Loss of a fetus in the first trimester is unlikely to adversely affect the surviving fetus or mother. No excess perinatal or maternal morbidity has been described resulting from a “vanishing” embryo.

Demise of a single fetus in a twin pregnancy after the first trimester is more common when they share a placenta, ranging in incidence from 0.5% to 6.8%, and may cause harm to the remaining fetus. Multiple fetuses (including twins) that share the same placenta have additional risks. Twin-twin transfusion syndrome in which there is an imbalance of circulation between the fetuses may occur in up to 20% of twins sharing a placenta. Excess or insufficient amniotic fluid may result from twin-to-twin transfusion syndrome. Twins sharing the same placenta have a higher frequency of birth defects compared to pregnancies having two placentas. Twins sharing the same placenta appear to occur more frequently after blastocyst transfer.

Placenta previa and vasa previa are more common complications in multiple gestations. Abruptio placenta also is more common and postpartum hemorrhage may complicate 12% of multifetal deliveries. Consequences of multiple gestations include the major sequelae of prematurity (cerebral palsy, retinopathy of prematurity, and chronic lung disease) as well as those of fetal growth restriction (polycythemia, hypoglycemia, necrotizing enterocolitis). It is unclear to what extent multiple gestations themselves affect neuro-behavioral development in the absence of these complications. Rearing of twins and high-order multiples may generate physical, emotional, and financial stresses, and the incidence of maternal depression and anxiety is increased in women raising multiples. At midchildhood, prematurely born offspring from multiple gestations have lower IQ scores, and multiple birth children have an increase in behavioral problems compared with singletons. It is not clear to what extent these risks are affected by IVF per se.

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Question 48. How successful is IVF?

Different physicians have different styles. I have always attempted to involve my patient's in the decision making process so that they look upon the treatment plan as their plan not my plan. Not all patients want this responsibility. Some look to the physician to run the show with little to no input. I always try to make my recommendation clear but I think that there are often alternative pathways.

For the past 4 years we have been promoting Natural Cycle IVF as an alternative pathway to traditional IVF. I believe that many clinics are unable to offer this approach effectively because of cost limitations and volume concerns. However, it certainly represents more of a finesse approach than that of stimulated cycle IVF. On the other hand, no arguing that stimulated cycle IVF has a higher pregnancy rate per initiated cycle and a low cancellation rate. On the other other hand, some patients are willing to trade off the cancellation rate in order to avoid taking fertility drugs....and so on...

So here is today's Question of the Day from the 2nd Edition of 100 Questions and Answers about Infertility. We are almost halfway there!


48. 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 (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). The paucity of clinics that offer Natural Cycle IVF is likely related to this reporting requirement. Natural cycle IVF can be an effective fertility treatment but the pregnancy rate will be less than for stimulated cycle IVF and the number of cancelled cycles will also be higher as patients may ovulate before egg collection, or fail to fertilize or fail to have a viable embryo to transfer.

Unfortunately, at the present time all IVF cycles are reported the same way with the CDC failing to segregate results from Natural Cycle IVF from stimulated cycle IVF. Needless to say, this reporting method does not encourage clinics to offer Natural Cycle IVF as the apparent IVF success rate will be reduced by the inclusion of Natural Cycle IVF in the calculations.

Table A: Factors influencing IVF success rates

1. Patient’s age
2. Type of infertility diagnosis
3. Duration of infertility (Best prognosis if <5yrs)
4. Experience/expertise of the clinic
5. Number of embryos transferred
6. Type of IVF performed: Stimulated vs. Natural Cycle IVF

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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Question 47. How do I know if I need IVF?

Although there are many paths to reproductive success, IVF is usually the fastest road to success. However, not all patients are thrilled about taking that road as the use of stimulation drugs can be intimidating to say the least. Our extensive experience in Natural Cycle IVF has been so encouraging that it makes one reassess how to counsel patients who are considering other options such as clomid/IUI or gonadotropin/IUI treatment cycles. Although our initial inclination was to encourage Natural Cycle IVF mainly in patients < 35 years old with well-defined fertility issues, our results suggest that success can be obtained in older patients and in those with unexplained infertility. Clearly pregnancy rates will be higher in patients < 40 years old but our current record holder was 47 years old with 4 failed stimulated cycle IVF attempts prior to achieving an ongoing pregnancy with Natural Cycle IVF. Go figure.

I spent over an hour on the phone with a reporter from NPR recently. She was very interested in Natural Cycle IVF and was considering running a piece on the topic. However, after speaking with some other local REs who were totally dismissive of Natural Cycle IVF she stopped answering my emails. Sad but true....good news doesn't sell papers or get listeners to stick with one radio station....and we believe that Natural Cycle IVF is very good news indeed!

So although the smug answer to the Question of the Day is that everyone needs IVF...they just don't know it yet.....here is a more balanced view.

47. 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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Question 46: What is IVF, and how is it performed?

Sometimes the first step is really the hardest in the entire journey. There is no doubt that IVF can be a roller coaster ride...physically, emotionally and psychologically. As physicians the best we can do is try to educate our patients so they can handle the ups and downs. Personally, I am really wimpy when it comes to riding roller coasters. At Universal Islands of Adventure my knees went weak at the site of the Hulk roller coaster and you can just forget any of the other big kid coasters. The best I can do is the little kid roller coaster as seen in this video. Those little girls thought it was so funny that I looked petrified but it's not my fault....it's my parents' fault for never taking me to Paragon Park in Nantasket Beach back in my formative years....



So as you consider the potential roller coaster ride of infertility treatment here is an overview of the IVF process from 100 Questions and Answers about Infertility, 2nd Edition.


46. 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 who was conceived using Natural Cycle IVF (NC-IVF). Since then, more than 4 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 glass” which translates to fertilization outside of the body in the laboratory. There are two types of IVF: 1) stimulated cycle IVF and 2) Natural Cycle IVF (NC IVF). We will focus on stimulated cycle IVF in this question but for more information on NC IVF please refer to many of the previous blog posts listed). 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. Louise Brown (the world’s first IVF baby) was produced in a natural cycle from a single follicle (NC IVF). Although a few clinics in the US (including our own) remain enthusisastic about NC IVF, most IVF in the USA is performed in a stimulated cycle using injectible fertility medications. The introduction of the medications (called gonadotropins) 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) and luteinizing hormone (LH) [Menopur] or (2) drugs containing only FSH (Bravelle, Gonal-F, Follistim) or LH (Luveris). 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, a 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 ultrasound results and blood hormone levels. Once the follicles reach a 20- to 24-mm diameter, the woman receives an injection of human chorionic gonadotropin (HCG; Pregnyl, Profasi, Novaryl) 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. Failure to take the hCG will result in an egg collection with apparently empty follicles as the eggs will not be ready for aspiration or eggs that are retrieved will be immature. Clearly, taking the hCG is absolutely critical which is why we check a blood test for hCG the morning after the shot to ensure that it was given correctly.

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. Some physicians use GnRH agonists (Lupron) instead of hCG to induce follicular maturation. This approach only works in patients who have not already been taking Lupron as part of their stimulation protocol.


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 egg collections at our office in a special procedure room, 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.

Phase 3: Embryo Culture
On the day following the egg collection, patients learn how many eggs were fertilized. Remember that although your RE measures all of the follicles during stimulation, mature eggs are usually found only in follicles with a diameter of more than 17 mm. In general, about 70% of the mature eggs will fertilize. Unfortunately, some attrition occurs at each point in an IVF cycle so the total number of healthy embryos is often much less than the original number of follicles or eggs.

Three days after the egg collection procedure, the embryos selected for embryo transfer will be identified. Allowing the embryos to grow for an additional 2-3 days in the laboratory may allow for enhanced embryo selection as some excellent appearing day 3 embryos will fail to continue to grow. Thus, implantation rates are usually higher for day 5-6 transfers because of this improved ability to select the best embryos. Additionally, there is some evidence that suggests waiting until day 5-6 may provide for improved synchronization of embryo and endometrium given that in nature the embryo usually doesn’t arrive in the uterus until day 5-6 after ovulation. On the day of embryo transfer your RE should review the quantity and quality of the embryos with the embryologist and then discuss with you his or her recommendations regarding the number of embryos to transfer.

Embryos that are not selected for transfer may still be of excellent quality, so they may be candidates for cryopreservation (freezing) with liquid nitrogen. These frozen embryos can then be replaced into the uterus during a future cycle, eliminating the need for the woman to undergo the entire IVF process of ovarian stimulation and egg collection. There is little benefit to freezing poor-quality embryos, however, because they are unlikely to result in a pregnancy and may not even survive the thawing process.


Phase 4: Embryo Transfer
Embryo transfer is one of the most critical aspects of an IVF cycle. During this phase, the embryos are transferred into the uterus by a procedure similar to an IUI. At our office, we perform our embryo transfers under abdominal ultrasound guidance to ensure the accurate placement of the embryos into the uterus. On the day of embryo transfer, patients are asked to drink 48 ounces of water and keep a full bladder to enable us to visualize the transfer of the embryos. No anesthesia is usually required for an embryo transfer and this step usually takes only 1-2 minutes to complete.

Phase 5: Post-Transfer and Pregnancy
During the 2 weeks after the embryo transfer, patients take supplemental progesterone (shots and/or suppositories). If a patient’s estrogen level drops significantly during the 2 weeks following embryo transfer, her physician may add supplemental estrogen as well.

Two weeks after the transfer, the woman typically undergoes a blood pregnancy test. Once a pregnancy test is positive, the physician may repeat the test every 2 days until the beta HCG level is high enough to visualize the pregnancy sac on transvaginal ultrasound (the beta HCG level should be more than 2000 IU around 3 to 4 weeks following embryo transfer). A follow-up ultrasound is then performed to confirm fetal cardiac activity. At this point, patients are usually referred back to their obstetrician/gynecologist for prenatal care.

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Question 45. How would I know when to pursue more advanced fertility treatments?

In the Kenny Rogers song the gambler there is a very famous line "you gotta know when to hold them, know when to fold them, know when to walk away, know when to run...." Sometimes I think about that line when counseling patients, but fortunately for them I never break out into song during a consultation. Deciding when to move onto more advanced treatments is a common concern among most fertility patients. Even those that start with IVF have to consider moving to donor egg/embryo if success is eluding us. I wish that I had that crystal ball to provide a glimpse into the future. That way I could advise patients "Don't worry, I know the 3rd IUI will work or the second clomid cycle or the first IVF or the FET or whatever.....But I don't have that ability...and if I did I would have used it to play the Powerball lottery and then it would be "see-ya later."

In general, most successful treatments will occur in the first 3-4 cycles of whatever treatment has been chosen. It can be hard to hold my tongue when a patient describes 18 months of continuous clomiphene or 9 clomid / IUI cycles or 7 FSH /IUI cycles etc etc.

No one wants to be a professional fertility patient....there just isn't any money in it. But seriously, most couples/individuals can only take so much disappointment before they throw in the towel and consider alternative paths to parenting. So if you don't have a Magic Eight Ball handy....how do you know when to "fold 'em" and move on.....well that is the Question of the Day from the 2nd Edition of 100 Questions and Answers about Infertility.

P.S. Princeton lost to Kentucky by 2 points.....oh well.


45. How would I know when to pursue more advanced fertility treatments?

The decision to seek out more advanced fertility treatments is a complex question, and multiple factors must be considered when making it. For most couples undergoing treatment with IUI (either alone or with fertility drugs), the best chances for success usually occur within the first four treatment cycles. After that, the likelihood for pregnancy decreases. In many of our patients, we recommend only one or two IUI treatments. If these efforts are unsuccessful, we suggest that the couple proceed with other more aggressive treatments including both Natural Cycle IVF and traditional IVF using injectible fertility medications.

For some patients, IUI should rarely be utilized. For example, those couples with severe tubal disease, severe endometriosis, pelvic adhesions, or severe male factor infertility may do best by directly proceeding with IVF as their first treatment option. If an age factor is present or if the couple has prolonged infertility (infertility lasting more than 5 years), we often recommend IVF first, as well. Remember that IVF is the only treatment for which even a failed treatment cycle provides some insight into a couple’s fertility potential. IVF does allow us to make some assessment of egg quality, fertilization and embryo development. A failed IUI cycle yields no such information as we only know that the cycle failed but learn nothing about fertilization, embryo growth or embryo quality.

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