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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