Your Fertility Pharmacist

Resources

Deeks J. When can odds ratios mislead? Odds ratios should be used only in case-control studies and logistic regression analyses. BMJ. 1998;317(7166):1155-1157. doi:10.1136/bmj.317.7166.1155a

Miranda ML, Edwards SE, Myers ER. Adverse birth outcomes among nulliparous vs. multiparous women. Public Health Rep. 2011;126(6):797-805. doi:10.1177/003335491112600605

Riwa S, Alison M, Ann K, et al. Pregnancy outcomes with increasing maternal age, greater than 40 years, in donor oocyte cycles. Hum Reprod. Published online March 20, 2025. doi:10.1093/humrep/deaf044

Talari K, Goyal M. Retrospective studies - utility and caveats. J R Coll Physicians Edinb. 2020;50(4):398-402. doi:10.4997/JRCPE.2020.409

Resources

Alemu BK, Wang CC, Li L, Zhu Z, Li Q, Wang Y. Effect of preconception antibiotics exposure on female reproductive health and pregnancy outcomes: a systematic review and meta-analysis. EClinicalMedicine. 2024;78:102935. Published 2024 Nov 22. doi:10.1016/j.eclinm.2024.102935

Shao S, Pan W, Wang B, et al. Association between antibiotic exposure and the risk of infertility in women of childbearing age: A case-control study. Ecotoxicol Environ Saf. 2023;249:114414. doi:10.1016/j.ecoenv.2022.114414

Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA,Thacker SB. Meta-analysis of observational studies in epidemiology: a proposal for reporting. JAMA 2000;283:2008-12.

Resources

Racicot K, Sakkas D, Barrett B, Chiang K, Jenkins C, Validation of a mailin delayed semen analysis protocol developed for home collection, F&S Reports (2024), doi: https:// doi.org/10.1016/j.xfre.2024.10.005.

ReproSource Semen Analysis At Home Collection Kit. https://www.reprosource.com/clinical-tests/at-home-collection-kit/ Accessed November 24, 2024.

This study compared efficacy of two r-FSH medications: follitropin alpha (Gonal-F) vs. follitropin beta (Puregon) on the number of live births cumulatively (CLBR). This was looking at patients 21-45yrs doing fresh embryo transfer after their first IVF or ICSI cycle.

Resources

Cao JX, Song JY. Follitropin Alpha versus Follitropin Beta in IVF/ICSI Cycle: A Retrospective Cohort Study. Drug Des Devel Ther. 2024;18:4359-4369. Published 2024 Sep 26. doi:10.2147/DDDT.S479700

Van den Haute L, Drakopoulos P, Verheyen G, De Vos M, Tournaye H, Blockeel C. Follitropin alpha versus beta in a first GnRH antagonist ICSI cycle: a retrospective cohort study. Reprod Biomed Online. 2021;43(4):655-662. doi:10.1016/j.rbmo.2021.06.014

New format with shorter episodes! A quick discussion on a survey sent to parents who conceived via IVF after preimplantation genetic testing (PGT).

The most rigorously designed trial of intraovarian PRP (to date) demonstrated no improvements in # of mature oocytes obtained or in # of live births versus placebo.

WHAT

• Comparison of intraovarian platelet-rich plasma (PRP) to placebo for improving the number of mature oocytes (MII) obtained after controlled ovarian stimulation in women with a history of poor ovarian response (POR) with in-vitro fertilization (IVF)

WHY

• Low to modest quality research has shown promising results with PRP for POR

• High-quality study is needed to assess the impact of PRP in IVF for POR

WHERE/WHEN

• Two academically affiliated reproductive centers (one in the USA and one in Turkey)

• January 2020 - November 2022

WHO

Inclusion Criteria:

• females ages 18-37 with POR defined as at least two IVF cycles cancelled due to poor follicle growth or just 0-2 follicles developing despite max FSH daily injections or 0-3 mature oocytes retrieved

• male partner must have 100k or greater total motile sperm count

Female Exclusion Criteria:

• BMI >35 kg/m2, surgically obtained sperm, or continued use of adjuncts that could result in improved ovarian response to treatment (specified CoQ10, DHEA, but presumably others per clinician’s discretion)

• for additional exclusion criteria, see p 2 within article

HOW

• Randomized at each site in 1:1 ratio via computer-generated block schema to PRP or no injection (control)

• Unblinded: patients + physicians performing PRP administration

• Blinded: physicians performing oocyte retrievals + physicians performing ultrasounds for antral follicle count (AFC) + all involved embryologists

• PRP group

  • sedated then received intraovarian 1 mL PRP injected into four ovarian sites between days 6-10 of menstrual cycle in cycle after study enrollment

  • Received (unspecified) antibiotics to prevent surgical infection

  • Estrace (oral estradiol) 2 mg BID x 25 days started on POD1 + Prometrium (oral progesterone) 200 mg BID x 10 days taken started 15 days later

• Control group started Estrace day after randomization and Prometrium 15 days later

• Embryos from both groups included ICSI, day 3 hatching, TE biopsies on Days 5-6-7 with subsequent PGT-A samples

• Euploid embryos transferred via frozen embryo transfer in subsequent menstrual cycle

• Pregnancies monitored at IVF clinic through eight weeks

• Used intention-to-treat analysis (ITT); tests varied by normality of distibution of variables

• Primary outcome = 0 for randomized patients who withdrew from study, who lacked mature oocytes, or had cycles cancelled

• Characteristics: 224 screened —> 112 eligible —> 87 enrolled —> 83 randomized into the two groups —> 76 proceeded with oocyte retrieval (PRP = 39, control = 37)

• Efficacy: no improvements found in markers of ovarian reserve (AMH, AFC), # mature oocytes retrieved, # blastocysts formed, or implantation rates with PRP vs. control

• Safety: no women experienced infections or hematomas with the PRP injection, though most of them were in mild discomfort for three days after getting PRP

• Increased rigor of this study design (inclusion of control group + randomization) may explain results that differ from previous PRP studies

• Additional strengths were validated PGT-A platform, strong patient adherence/retention, and stringent inclusion criteria

• Study limitations were PRP prep is not necessarily universally generalizable (though used commercially available product), PRP composition was not analyzed, randomization method might have been predictable, and results not generalizable beyond POR

• PRP will not improve IVF results in POR

  Conclusions

This is the highest-quality PRP trial conducted thus far, which randomized, blinded, and compared PRP injections to no injections in infertile women with poor ovarian response. Results showed that PRP does not improve fertility markers nor outcomes compared to not giving the PRP. Future studies should be conducted with similar methodology (but recruiting additional participants at more study sites) to confirm results, especially since the results from this study conflict with previous, albeit lower-quality studies.

Resources

Cakiroglu Y, Yuceturk A, Karaosmanoglu O, et al. Ovarian reserve parameters and IVF outcomes in 510 women with poor ovarian response (POR) treated with intraovarian injection of autologous platelet rich plasma (PRP). Aging (Albany NY). 2022;14(6):2513-2523. doi:10.18632/aging.203972

Herlihy NS, Cakiroglu Y, Whitehead C, et al. Effect of intraovarian platelet-rich plasma injection on IVF outcomes in women with poor ovarian response: the PROVA randomized controlled trial. Hum Reprod. Published online May 9, 2024. doi:10.1093/humrep/deae093

Food and Drug Administration. BK210591 - Platelet-Rich Plasma (PRP) Procedure Pack. Accessed September 7, 2024. BK210591 - Platelet-Rich Plasma (PRP) Procedure Pack | FDA

Resources

Bronson R. and Kruljac I, Butorac D, Vrkljan M. and Legro RS, Zhang H; Eunice Kennedy Shriver NICHD Reproductive Medicine Network. Letrozole or clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med. 2014;371(15):1463-1464. doi:10.1056/NEJMc1409550

Centers for Disease Control and Prevention. PCOS (Polycystic Ovary Syndrome) and Diabetes. https://www.cdc.gov/diabetes/basics/pcos.html. Accessed April 21, 2024.

Franik S, Kremer JA, Nelen WL, Farquhar C. Aromatase inhibitors for subfertile women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2014;(2):CD010287. Published 2014 Feb 24. doi:10.1002/14651858.CD010287.pub2

Franik S, Le QK, Kremer JA, Kiesel L, Farquhar C. Aromatase inhibitors (letrozole) for ovulation induction in infertile women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2022;9(9):CD010287. Published 2022 Sep 27. doi:10.1002/14651858.CD010287.pub4

Legro RS, Brzyski RG, Diamond MP, et al. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome [published correction appears in N Engl J Med. 2014 Oct 9;317(15):1465]. N Engl J Med. 2014;371(2):119-129. doi:10.1056/NEJMoa1313517

Legro RS, Diamond MP, Coutifaris C, et al. Pregnancy registry: three-year follow-up of children conceived from letrozole, clomiphene, or gonadotropins. Fertil Steril. 2020;113(5):1005-1013. doi:10.1016/j.fertnstert.2019.12.023

Palomba S, Santagni S, Falbo A, La Sala GB. Complications and challenges associated with polycystic ovary syndrome: current perspectives. Int J Womens Health. 2015;7:745-763
https://doi.org/10.2147/IJWH.S70314

World Health Organization. Polycystic Ovary Syndrome. World Health Organization; 2023. Accessed April 21, 2024. https://www.who.int/news-room/fact-sheets/detail/polycystic-ovary-syndrome

Zhang H. Pregnancy in Polycystic Ovary Syndrome II (PPCOSII). ClinicalTrials.gov identifier: NCT00719186 . Updated June 14, 2018. Accessed April 20, 2020. https://classic.clinicaltrials.gov/ct2/show/NCT00719186

A new study examines the associations between COVID-19 infection with pregnancy and miscarriage rates, looking at the first ten weeks after fresh embryo transfer.

A study compared fertility and sexual markers in obese men with low testosterone and erectile dysfunction who took liraglutide, uFSH + HCG, or testosterone. These men were separated into three groups based on their plans for parenthood; results showed impressive improvements on the GLP-1 agonist liraglutide.

Resources

Giagulli VA, Carbone MD, Ramunni MI, et al. Adding liraglutide to lifestyle changes, metformin and testosterone therapy boosts erectile function in diabetic obese men with overt hypogonadism. Andrology. 2015;3(6):1094-1103. doi:10.1111/andr.12099

Jensterle M, Podbregar A, Goricar K, Gregoric N, Janez A. Effects of liraglutide on obesity-associated functional hypogonadism in men. Endocr Connect. 2019;8(3):195-202. doi:10.1530/EC-18-0514

Latif W, Lambrinos KJ, Rodriguez R. Compare and Contrast the Glucagon-Like Peptide-1 Receptor Agonists (GLP1RAs). In: StatPearls. Treasure Island (FL): StatPearls Publishing; March 27, 2023.

La Vignera S, Condorelli RA, Calogero AE, Cannarella R, Aversa A. Sexual and Reproductive Outcomes in Obese Fertile Men with Functional Hypogonadism after Treatment with Liraglutide: Preliminary Results. J Clin Med. 2023;12(2):672. Published 2023 Jan 14. doi:10.3390/jcm12020672

Papadakis G. Sex Steroids Balance for Metabolic and Reproductive Health in Klinefelter Syndrome (KLIN-HEALTH). ClinicalTrials.gov identifier: NCT05586802. Updated April 4, 2023. Accessed September 27, 2023. https://www.clinicaltrials.gov/ct2/show/NCT05586802

A recent study compared GnRH antagonists in egg donor ovarian stimulation cycles. The first drug is a newer agent, elagolix (Orilissa), that is taken as a tablet at night. The older drug is an injectable agent called ganirelix (Fyremadel). How did Orilissa stack up in terms of eggs retrieved and embryos formed vs. ganirelix? Were there adverse events, like ovarian hyperstimulation or early LH surge? Results explored in this episode and what they mean for upcoming egg donor cycles.

Resources

Boniface C, Schnorr JN, Gray J, et al. The role of elagolix in the suppression of ovulation in donor oocyte cycles. F S Rep. 2023;4(2):179-182. Published 2023 Mar 25. doi:10.1016/j.xfre.2023.03.006

Check JH, Brasile D, Choe JK, Amui J, Wilson C. The effect of cetrorelix vs. ganirelix on pregnancy outcome using minimal gonadotropin stimulation in women with elevated day 3 serum follicle stimulating hormone levels. Clin Exp Obstet Gynecol. 2009;36(3):148-149.

Fyremadel [package insert]. Parsippany, NJ: Ferring Pharmaceuticals, Inc.; 2022. manufactured by Sun Pharma (India)

Kay, C. Contaminated Drugs, Shredded Papers: US FDA Uncovers Failures in India Pharma Factories. May 31, 2013. Accessed July 11, 2023. https://www.bloomberg.com/news/articles/2023-05-31/us-finds-contaminated-drugs-further-lapses-in-india-pharma-factories-post-covid#xj4y7vzkg

Keenan, J. Sun Pharma pauses US drug exports from India plant after FDA scolding. April 27, 2023. Accessed July 10, 2023. https://www.fiercepharma.com/manufacturing/sun-pharma-hits-pause-mohali-plant-response-fda-letter/

Orilissa [package insert]. North Chicago, IL: Abbvie; 2021.

Zhang J, Zhou X, Chen Y, et al. Nan Fang Yi Ke Da Xue Xue Bao. 2019;39(10):1207-1212. doi:10.12122/j.issn.1673-4254.2019.10.12