Starting or continuing the IVF journey can feel like information overload — success rates, drugs, “add-ons”, lifestyle tweaks… it’s a lot. This guide brings together what the evidence actually shows, explained in a clear and compassionate way, so you feel more confident and informed.
Clomid and Letrozole: Where They Fit In
Before full IVF, many people are offered oral medications to help stimulate ovulation.
- Clomid (clomiphene citrate) has been around for decades. It works by nudging your brain to send stronger signals to the ovaries.
- Around 70–80% of women will ovulate on Clomid, but only about half of those will conceive.
- Per cycle, the chance of pregnancy is often around 10–12% — so it can take a few tries, and success builds across multiple cycles.
- One downside: Clomid can sometimes thin the uterine lining or affect cervical mucus.
- Letrozole, originally a breast cancer drug, is now widely used for fertility, especially in PCOS.
- Studies show higher ovulation and live birth rates compared to Clomid (for example, one large trial found live birth rates of 27.5% for letrozole vs. 19.1% for Clomid in PCOS).
- Letrozole also carries a lower risk of multiples and tends to be gentler on the endometrium.
- In many clinics, it’s now the first choice over Clomid.
These medications are usually tried before IVF, or as part of a mild stimulation IVF protocol. They’re less powerful than injectable gonadotropins used in standard IVF, but they can be a helpful step — especially in women with irregular cycles or PCOS.
IVF Success Rates: The Big Picture
- First-time IVF: In the UK, live birth per embryo transfer with own eggs is around 35% for ages 18–34, dropping to 10% at 40–42, and about 5% at 43–44.
- Cumulative success: Your chances add up over several transfers from one egg collection, so the odds of taking home a baby are higher than the “per cycle” figure.
- Donor eggs: Using donor eggs largely overcomes the effect of age on egg quality — success rates are much higher even for women in their 40s.
Embryo Grading and Transfer Timing
- Grading: A “beautiful” embryo is not always the winner, and some “average-looking” ones become healthy babies. Grading gives clues but isn’t perfect.
- Day-3 vs. Day-5 transfers: Day-5 (blastocyst) transfers can give higher success per transfer, but across a whole IVF cycle plan, outcomes can be very similar. The best choice depends on how many embryos you have and your clinic’s results.
- Single vs. double embryo transfer: Transferring one embryo at a time is usually safest, as twins carry higher risks for both mother and babies.
PGT-A Testing: What Is It and Who Might Benefit?
- PGT-A (Pre-implantation Genetic Testing for Aneuploidy) checks whether embryos have the correct number of chromosomes before transfer.
- A few cells are taken from the embryo’s outer layer and tested.
- Only embryos that look chromosomally “normal” are selected for transfer.
- What the research says:
- Miscarriage: PGT-A reduces miscarriage, especially in women over 35.
- Per transfer success: Some studies show higher pregnancy and live birth per transfer in older women or those with recurrent miscarriage.
- Cumulative live birth (total babies per cycle): For younger women with many embryos, PGT-A doesn’t clearly improve — and can even reduce success if embryos labelled “abnormal” are discarded.
- Who might benefit:
- Women over 37–38 with multiple embryos.
- Couples with recurrent pregnancy loss.
- Those who want to reduce the emotional cost of miscarriage.
- Who may not need it:
- Younger women with good prognosis.
- Couples with only a few embryos, where testing may leave none to transfer.
- Key point: PGT-A is a tool, not a guarantee. It can be helpful for some, but it doesn’t increase the overall chance of a baby for everyone.
Progesterone: Vaginal, Injection, or Rectal?
Progesterone support is essential after IVF. The good news is: all the common forms work.
- Vaginal gels/capsules, injections (IM or subcutaneous), and even rectal progesterone have all been shown to be effective.
- The key is choosing the route you can use consistently and comfortably.
Lifestyle and “Holistic” Approaches That Actually Help
Some things are gentle, low-risk, and supported by research:
- Mediterranean-style eating: Linked with better IVF outcomes and great for overall health.
- Vitamin D: If you’re low, topping up may improve IVF success.
- CoQ10 (ubiquinol): May help women with low ovarian reserve respond better.
- Mind–body programmes: Stress reduction, yoga, and mindfulness lower anxiety and may boost success.
- Acupuncture: The evidence is mixed, but many find it calming.
Medications and Add-Ons: What’s Worth Considering?
- Metformin: Useful for women with PCOS, especially to lower risk of OHSS.
- Growth hormone (GH): Sometimes used for “poor responders,” though results are mixed.
- DHEA: May support women with diminished ovarian reserve, but should only be used under specialist guidance.
- Aspirin, steroids, or “immune” treatments: Not recommended unless you have a specific diagnosis.
Sperm Selection
- PICSI (selecting sperm that bind to hyaluronic acid) may reduce miscarriage and help in certain cases.
- Microfluidics (sorting sperm through channels) reduces DNA damage and looks promising, though bigger trials are ongoing.
Pulling It Together
If you’re just starting out, Clomid or Letrozole may be offered before IVF with Letrozole often the gentler, more effective option.
If you’re moving into IVF, remember: age and egg quality are the biggest drivers, but supportive lifestyle choices, the right progesterone, and thoughtful use of add-ons can all make a difference.
PGT-A testing is useful in certain groups but not a universal “must-have.”
IVF can feel clinical, but surrounding yourself with compassionate care nutrition, relaxation, mind–body support can make the journey softer and more sustainable.
Kindness takeaway: There is no “magic bullet,” but there are many small, evidence-backed choices that add up. Focus on what you can influence, ask questions, and let yourself be supported along the way.
References
American Society for Reproductive Medicine (ASRM). (2024). The use of preimplantation genetic testing for aneuploidy: A committee opinion. Retrieved from https://www.asrm.org/practice-guidance/practice-committee-documents/the-use-of-preimplantation-genetic-testing-for-aneuploidy-a-committee-opinion-2024/
Legro, R. S., Brzyski, R. G., Diamond, M. P., Coutifaris, C., Schlaff, W. D., Casson, P., … & NICHD Reproductive Medicine Network. (2014). Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. New England Journal of Medicine, 371(2), 119–129. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175743/
Liu, W., Gong, F., Li, J., Lin, X., He, L., Zhang, S., & Lin, X. (2014). Letrozole versus clomiphene citrate for unexplained infertility: A systematic review and meta-analysis. Journal of Obstetrics and Gynaecology Research, 40(3), 701–710. https://pubmed.ncbi.nlm.nih.gov/24754848/
Münne, S., Kaplan, B., Frattarelli, J. L., Katz-Jaffe, M., Tilia, L., Treff, N. R., … & STAR Study Group. (2019). Preimplantation genetic testing for aneuploidy versus morphology as selection criteria for single frozen-thawed embryo transfer in good-prognosis patients: A multicentre randomized controlled trial. New England Journal of Medicine, 380(2), 163–173. https://www.obg.cuhk.edu.hk/wp-content/uploads/yan-birth-PGT-A-nejm-2021.pdf
National Institute of Child Health and Human Development (NICHD). (2015). The AMIGOS trial: Letrozole, gonadotropin, or clomiphene for unexplained infertility. New England Journal of Medicine, 373(13), 1230–1240. Summary available at https://www.2minutemedicine.com/letrozole-linked-to-lower-rate-of-multiple-gestation-and-live-birth-vs-gonadotropin-the-amigos-study/
Yan, J., Qin, Y., Zhao, H., Sun, Y., Gong, F., Li, R., … & Qiao, J. (2021). Live birth with or without preimplantation genetic testing for aneuploidy. New England Journal of Medicine, 385(22), 2047–2058. https://www.obg.cuhk.edu.hk/wp-content/uploads/yan-birth-PGT-A-nejm-2021.pdf
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