No matter when you google “in vitro fertilization” (IVF) “egg freezing,” or “egg donation,” you’re always bound to come across several recent headlines, whether they’re about celebrities discussing how expensive IVF is and how many rounds they’ve undergone; companies releasing new AI tools to predict IVF success; or other companies promising egg freezing for free when women decide to donate half of their eggs to others.
For decades, IVF has been touted as the go-to procedure for infertility, medical students and Ivy League grads have been enticed to donate their eggs for large sums, and egg freezing has (more recently) been touted as a panacea for protecting one’s future fertility. However, what we’re not often told about are the risks that come along with that first critical step—the egg retrieval procedure—even though knowledge of these risks is vital for true informed consent. In this article, we’ll cover the procedures and drugs involved in the egg retrieval process, and the risks that accompany them.
Gonadotropins and ovarian stimulation
The egg retrieval process—arguably better termed egg “harvesting” than “retrieval”—first involves stimulating the follicles (the tiny, fluid-filled sacs containing eggs inside the ovary) through the use of medications called gonadotropins, which help the ovaries to produce multiple fully mature follicles at once—a process known as controlled ovarian hyperstimulation (COH)—in the hopes that multiple eggs can be obtained for future use in IVF.
In a natural menstrual cycle, gonadotropins are released by the pituitary gland every month. These naturally occurring gonadotropins include follicle stimulating hormone (FSH) and luteinizing hormone (LH), which facilitate the maturation of several follicles in preparation for the release of an egg (ovulation) from the ovary (although, typically, only one follicle will fully mature to the point of rupture, or ovulation). In the IVF process, synthetic versions of FSH and LH are administered, sometimes in a combination medication containing both FSH and LH. Some side effects of gonadotropins include blood clots, Ovarian Hyperstimulation Syndrome (OHSS—more on this below), ectopic pregnancies, and ovarian torsion (a twisting of the ovaries due to heavier-than-usual follicles, which is a medical emergency that can result in the loss of an ovary) [1].
Unfortunately, there are few studies on the long-term impacts of these synthetic hormones on the body, so the full breadth of their risks is unknown, though some studies have shown a possible increase in ovarian and breast cancers following the use of fertility medications [2] [3].
GnRH agonists and antagonists
Sometimes, a GnRH (gonadotropin releasing hormone) agonist is used for a few days instead of synthetic FSH and LH to stimulate the pituitary gland to release its own FSH and LH gonadotropins. However, after 7-10 days, GnRH actually begins to suppress the production of any further FSH and LH, and there is evidence that prolonged suppression of natural gonadotropins can lead to cardiovascular issues such as hypertension and stroke.
Since reproductive endocrinologists must collect multiple eggs for IVF before they are ovulated into the fallopian tube, a GnRH antagonist is given to prevent ovulation occurring before the scheduled day of retrieval. Unlike GnRH agonists, GnRH antagonists work immediately to block the receptors in the pituitary gland that release gonadotropins, so these are often used for preventing ovulation. As with the use of gonadotropins, an insufficient number of studies have been conducted to show the side effects of agonists’ and antagonists’ impacts on the pituitary gland.
Next, a shot to trigger ovulation is given, which could include: shots of human chorionic gonadotropin (hCG, or the hormone that helps maintain early pregnancy); a combination of hCG and the drug Lupron to reduce risk of ovarian hyperstimulation syndrome; or only Lupron for women whose risk of OHSS is so great (like those with PCOS) that they cannot tolerate even the small dose of hCG that is present in the combination shot [4]. However, the risk of OHSS isn’t completely eliminated with the combination or Lupron-only trigger shot [5].
Ovarian hyperstimulation syndrome (OHSS)
Ovarian hyperstimulation syndrome occurs when ovaries respond too strongly to the stimulating medications used in the retrieval process, causing excessive swelling of the follicles and the leakage of fluids from the ovaries into the abdomen. Symptoms of OHSS can include blood clots, kidney dysfunction, dehydration, shallow pulse, nausea, vomiting, and shortness of breath.
Even though Lupron decreases the risk of ovarian hyperstimulation syndrome, moderate-to-severe OHSS has still been shown to occur in around 1-5% of IVF cycles. To put that number into perspective, according to the American Society for Reproductive Medicine, there were approximately 432,641 IVF cycles in 2023, which calculates to between 4,326 to 21,632 women developing OHSS. Furthermore, even though Lupron is used as a precaution against OHSS, the drug comes with its own risks, including chest pain, shortness of breath, blood clots, heart attack or heart failure, severe skin reactions, seizures, and loss of bone density, among several other risks.
… moderate-to-severe OHSS has still been shown to occur in around 1-5% of IVF cycles. To put that number into perspective, according to the American Society for Reproductive Medicine, there were approximately 432,641 IVF cycles in 2023, which calculates to between 4,326 to 21,632 women developing OHSS.
The role of hormonal contraceptives in IVF egg retrieval
In addition to synthetic FSH, LH, Lupron, etc., birth control pills may also be used in the controlled ovarian hyperstimulation process to control the timing of the retrieval procedure, and/or to prevent the natural growth of follicles in order to establish a “baseline” with which to start the follicle stimulation process through externally administered gonadotropins.
The use of hormonal contraceptives may also reduce the likelihood of ovarian cysts developing during the hyperstimulation process, and ASRM notes that hormonal contraceptives may also increase IVF success rates in those with polycystic ovary syndrome and endometriosis. However, birth control pills use synthetic forms of progesterone and estrogen, or hormones that are not bioidentical to ones naturally produced by the body, called progestin and estradiol. The use of synthetic hormones can have negative effects on the body, such as heart attack, stroke, breast and cervical cancer, mood changes, breakthrough bleeding, a decrease in bone density, autoimmune disorders, and weight gain.
Hormonal contraceptives also come with an increased risk of developing blood clots. As one systematic review on contraceptives and blood clots reported:
…using HC increases a woman’s risk of being diagnosed with VTE (venous thromboembolism) by three to nine times. For women under 30, the risk is increased 13-fold during the first year of use, when the risk for clot formation is highest.” The study also found that “…the risk of fatal VTE was increased in women aged fifteen to twenty-four by 18.8-fold [6].
Further, the synthetic hormones in contraceptives can literally alter the functioning of parts of the brain such as the ventromedial prefrontal cortex, the part of the brain that’s responsible for decision-making, emotional regulation, and memory. One study found that women using hormonal contraceptives had greater susceptibility to chronic anxiety and greater overall fearfulness because of a thinning of the tissue in the brain that correlates with one’s ability to handle generalized fear, mental and emotional resilience, and the ability to stay calm.
Egg retrieval and embryo transfer
After the controlled ovarian hyperstimulation process comes the egg retrieval procedure. A very fine needle is inserted into the vagina and used to pierce through the vaginal wall to access the ovaries. The needle then punctures each of the swollen follicles to remove their egg-containing fluid.
While the long-term risks of egg retrieval are not well-documented, (arguably making it difficult for a patient to give true informed consent to the procedure), the reported short-term risks of egg retrieval include: accidental puncturing of the bladder, intestines, uterus, ovaries, and blood vessels by the needle; as well as the risk of pelvic and ovarian infections; inflammation in the lining of the abdominal cavity; pelvic abscesses; ovarian twisting; abdominal bleeding; and anesthesia complications [7].
Regarding the embryo transfer process, or when the retrieved eggs have been successfully fertilized with sperm in the lab and one (or two) of the resulting embryos are transferred into the woman’s uterus, a few surgical complications that can arise during the procedure include: bleeding into the uterine cavity or perforation of uterine muscles following catheter insertion; and/or pelvic infections [8].
Likelihood of egg retrieval success
Women seeking to harvest their eggs for immediate IVF or for egg freezing for future IVF may have to endure multiple cycles, since not every egg extracted will be mature enough to fertilize, and then, only about 80% of the remaining eggs will fertilize. After successful fertilization, women under 35 have a success rate of 40-50% live birth per embryo transfer, women aged 35-37 have a success rate of 30-35%, and the success rate continues to decrease with increasing age.
Fortunately, IVF is not the only means of overcoming infertility. Couples struggling to conceive may also consider addressing the root causes of their fertility issues through the use of Fertility Awareness Methods (FAMs) and Restorative Reproductive Medicine (RRM) procedures, which aim to improve overall health in addition to increasing fertility.
