This is the 5th in a series of 10 responses to common questions/concerns about IVF

#5: How Painful and/or Risky are the Injections of Fertility Drugs, the Egg Retrieval (ER) and the Embryo Transfer (ET)?

No one likes getting injections, but with IVF there will inevitably be a lot of these. The good news is that most of the injections are water soluble and administered in small amounts via a short thin needle subcutaneously (just under the skin) and are thus less painful than others that are given deep in the muscle (intramuscular) Agonists such as Lupron and Buserilin; antagonists such as Ganirelix, Orgalutron and Cetrotide; gonadotropins such as Follistim, Gonal F, Puregon, and Luveris are all given subcutaneously and are thus usually well tolerated.

In contrast, certain injections are oil based, are rather viscous and thus do not disperse easily once injected, causing discomfort. The two notable examples are estradiol valerate in oil (Delestrogen) and progesterone in oil (PIO). Delestrogen is given twice weekly but in very small amounts and thus does not pose nearly as much of a problem as does PIO. This is administered starting with the egg retrieval (in conventional IVF cycles). In cases of embryo recipients (frozen embryo transfers [FET], egg donation, gestational surrogacy and embryo donation) it is commenced starting about 5 days prior to embryo transfer (ET) and in both situations, is continued until near the end of the first trimester.

In some cases the woman can be allergic to the type of oil used in the injected medication. In the case of PIO there are several different types of oil used (e.g., sesame, peanut, ethyl oleate and olive oil). When there is a local reaction to one type of oil, another can be tried. When Delestrogen-oil causes a reaction it can be supplanted with estrogen skin patches (though suboptimal). In the case of PIO reactions, one can switch to a vaginal administration of progesterone (e.g., Endometrin, Crinone, etc.). While effective in non-hormone-recipient cycles, in my opinion, vaginal preparations are less than optimal in the case of embryo recipients.

Severe, life endangering anaphylactic reactions are extremely rare in response to the administration of any of these hormone preparations.

In some cases, an inadequately sterile technique when administering fertility drugs will lead to infection at the site of injection and in some cases (very rarely) to abscess formation. Also, because the injection of PIO is given in the upper outer quadrant of the buttock, there is a small risk of traumatizing the sciatic nerve. This can lead to pain that radiates down the back of the leg and goes away after several days. Sometimes the needle will inadvertently break a small blood vessel, which can lead to a hematoma and bruising. However, it will rarely be severe enough to require medical intervention.

Not surprisingly, the use of any hormonal preparation can evoke side effects, and fertility drugs are no exception. The hormonal changes elicited by the gonadotropins can result in emotional volatility. In my experience, women tend to experience an exaggeration of their underlying demeanor – whether it be optimistic or pessimistic.

The side effects of the various medications used have been dealt with in other posts on this site. One of the most serious of these is Severe Ovarian Hyperstimulation Syndrome (OHSS) which can be life endangering, but which only occurs after the administration of the hCG trigger. OHSS can be prevented through judicious treatment. Please refer to the article HERE relating to OHSS for more details.

The Egg Retrieval
It should go without saying that any surgical procedure performed under conscious sedation carries with it certain anesthesia-related risks as well as surgical risks relating to infection, bleeding and damage to surrounding structures. However, having performed thousands of egg retrievals, I can say with confidence that the risk of serious complications is extremely low indeed. In fact, I can count on one hand the number of times over a period of approximately 30 years that I’ve had to admit a patient to the hospital because of a serious complication arising at the time of egg retrieval.

The biggest danger occurs in women who have a bleeding tendency that goes undetected. This is why it is so important to rule this out before proceeding to egg retrieval. One word of caution is that medications such as aspirin, and certain non-steroidal analgesics such as Motrin and Advil can prolong the bleeding time and increase the risk of hemorrhage. Accordingly, such medications should be avoided for approximately 5 days prior to the egg retrieval.

Clearly, any procedure involving penetrating the nerve-rich capsule of the ovary (as with egg retrieval) will result in some discomfort. The bigger problem is that after extracting follicular fluid the follicle often fills and over-distends with blood, thereby stretching the ovarian capsule and causing post operative pain. This does not generally reach the point of severe discomfort in most cases, but it can. In addition, the nerve reaction so evoked sometimes causes post operative vomiting, sweating and even diarrhea. In most cases, an egg retrieval will result in some bleeding within the pelvic cavity (the blood usually collects behind the uterus, in the lower most point in the abdominal cavity, i.e., the cul de sac). Most IVF physicians will intentionally aspirate as much of this blood as possible because it can be the source of pain.

It has been my practice to inject a dilution of a long-acting local anesthetic into the pelvic cavity at the conclusion of egg retrievals performed on women who for whatever reason are not planning to have an embryo transfer done in the same cycle. Examples include egg donors, women using a gestational surrogate, and those banking their eggs or embryos for future dispensation. This must be done cautiously, avoiding a direct injection of the local anesthetic into a blood vessel because this can cause complications. However, if done carefully, the local anesthetic will numb the nerves on the membrane that envelops the ovaries, uterus, fallopian tubes, bowel and other pelvic structures, thereby reducing post operative pain for at least 4-6 hours.

The Embryo Transfer
With rare exceptions, the embryo transfer (ET) is a painless procedure. However, sometimes the cervical canal through which the ET catheter must traverse to deliver the embryos into the uterine cavity, is constricted (stenosed), tortuous or has lesions growing in it that obstruct the passage of the catheter. In some such cases, it is necessary to introduce a probe or a thin dilator through the cervical canal in order to create a clear passage into the uterus. This can cause pain and, on rare occasions, evoke a severe and potentially dangerous, abrupt autonomic (nerve-related) response. When this happens, the woman’s blood pressure will drop precipitously, she will have a slow and thready heartbeat and she might even collapse or convulse. While this is very rare, it is something that all IVF doctors must be on the lookout for. Accordingly, at times, when a prior “mock embryo transfer” (performed some days prior to the planned embryo transfer) suggests that the ET will be difficult, it is best to perform the procedure under conscious sedation with an anesthesiologist present.

Occasionally, it is not possible to traverse the cervical canal with a catheter. In such cases (fortunately very rarely) the patient must undergo a transmyometrial embryo transfer procedure. Here, with the woman under conscious sedation and using sterile technique, a relatively wide bore needle is passed vaginally (under ultrasound guidance) through the uterine wall into the endometrial cavity. A thin catheter is passed through this needle and the embryos are so delivered. This transmyometrial procedure uses a very special delivery system and can be very effective, but it requires significant expertise. I personally have performed about 20 such procedures over the years.

One of the most frequent complaints I encounter with the performance of embryo transfers is a result of the fact that in order to perform the procedure efficiently, it is necessary that the bladder be filled in advance. This causes varying degrees of discomfort, because some women’s bladders fill quickly and over distend, while others take a longer period of time. As a result, it is very difficult to time the ET procedure so as to correspond with optimal but not over distention of the bladder. In most cases, this can be accomplished through repeated abdominal ultrasound examinations, but it is not always so. I cannot tell you how many times I have been chastised for causing the woman discomfort by unnecessarily delaying the embryo transfer to the point that her bladder becomes over-distended. This is a tough problem to avoid, but I wish to emphasize how important it is that the bladder be adequately filled so as to allow for proper visualization of the uterine lining. Without this ability, it is impossible to efficiently deliver the embryos into the uterus.

Some degree of discomfort through the various phases of performing an IVF cycle is inevitable. For reasons cited above, some women experience more discomfort than others. I have found that proper disclosure and counseling in advance of performing a procedure prepares the woman and her partner for this likelihood and goes a long way towards achieving patience, tolerance and appreciation. Furthermore, it enhances the doctor-patient relationship. Nothing is harder for any IVF physician to deal with than a disgruntled patient who does not get pregnant in the end. And of course, no one can guarantee a successful outcome. It follows that it is very important to try and establish and maintain the best possible doctor-patient relationship at all times.