352 ‒ Female fertility: reproductive health, treating infertility & PCOS, and the IVF process

Paula stressed that many women with PCOS are simply put on the pill without understanding why, which she sees as a missed educational opportunity. The primary goal is to avoid long intervals of unopposed estrogen that can overstimulate the endometrium. The pill is highly effective for cycle regulation and hyperandrogenic symptoms. She acknowledged that for those who are overweight, the first step should be weight loss, and GLP-1 agonists are increasingly used but cannot be taken while actively trying to conceive because safety data are lacking.

Paula described how she first checks that the woman has had a period; if not, she gives a course of progesterone, and withdrawal bleeding is designated day 1. She then starts letrozole on days 3–5, usually for five days. Around day 12 she performs an ultrasound to see follicle development. If no response, the dose is increased. For women who are young and have just started ovulating, she may continue the treatment for more than three cycles. If no ovulation occurs after three cycles of letrozole (and clomid if tried), she would move to injectable gonadotropins or directly to IVF, because injectable + IUI carries a high multiple pregnancy rate and approaches IVF cost.

Paula walked through the entire IVF timeline: birth control pill for 2 weeks to quiet the ovaries, stop, then daily injections of gonadotropins (FSH + a small amount of LH). Every few days the patient comes for ultrasound and estradiol measurement. Once follicles reach approximately 18–22 mm, she administers hCG. Egg retrieval is scheduled exactly 36 hours later. She described the retrieval as a transvaginal, ultrasound-guided needle aspiration under propofol sedation, taking 30 minutes. The embryologist immediately examines the aspirated fluid to identify oocytes. She emphasised that the lab environment is critical: culture media, temperature, and gas conditions are carefully controlled to mimic the fallopian tube.

Paula detailed that after retrieval, about 70% of eggs fertilise, and then about half of those reach blastocyst stage. The ones that arrest are presumed chromosomally abnormal. She noted that many clinics now routinely offer PGT-A, but she believes patients should be counselled about the pros and cons rather than it being mandatory. The primary benefit is avoiding the transfer of aneuploid embryos that would miscarry or fail. The controversy stems from studies suggesting some embryos labelled abnormal due to mosaic results might self-correct after transfer. She emphasised that morphology is a complementary criterion, and that a good embryologist is essential for accurate biopsy and interpretation.

Paula explained that if a young woman (e.g., 20) asks about egg freezing, she would advise against it because the vast majority will never need those eggs. The cost-effectiveness sweet spot is early- to mid-30s, when ovarian reserve is still reasonably good but the probability of eventually needing assistance is higher. She underscored that egg freezing is not an insurance policy but a proactive step, and that even among women who use their frozen eggs and don’t achieve pregnancy, the psychological benefit of having done something is noted in studies. She also emphasised the need for societal changes to make it easier to have children during peak reproductive years.

Paula explained that a randomized controlled trial compared letrozole (Femara) head-to-head with clomiphene in PCOS patients and showed a statistically higher pregnancy rate with letrozole. The mechanism is paradoxical: by blocking the conversion of androgens to estrogen via aromatase inhibition, the drop in estrogen feedback triggers increased pituitary secretion of FSH and LH, stimulating follicular development. She noted that many general gynaecologists do not have the setup for ultrasound monitoring, but the medication is cheap and can still be prescribed alongside other ovulation tracking methods. The advantage is a more physiologic recruitment of a single dominant follicle, reducing the risk of multiples compared to high-dose gonadotropins.

Paula stated that in cases of very low sperm count, poor motility, or abnormal morphology, ICSI is clearly indicated. However, many clinics adopt ICSI universally because a small percentage of couples experience complete fertilisation failure with conventional IVF, and that is a catastrophic outcome—you lose all retrieved eggs for that cycle. She acknowledged the controversy and the added cost, noting that for non-male factor the success rates are equivalent between ICSI and conventional IVF, but the fear of zero fertilization drives practice patterns.

Paula explained that the concept comes from mouse studies showing rapamycin might reduce the programmed death of egg cells (atresia), thus preserving ovarian reserve. The Columbia trial is giving 5 mg daily for a few months and measuring AMH before and after. She expressed skepticism: a positive result would be intriguing but a negative result wouldn't rule out a long-term benefit, and the study does not directly assess fertility or pregnancy. She warned that rapamycin is immunosuppressive and not recommended for anyone trying to conceive outside a study.