Your Fertility Pharmacist

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.ResourcesCao 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.S479700Van 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

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

ResourcesBronson 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/NEJMc1409550Centers 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.pub2Franik 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.pub4Legro 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/NEJMoa1313517Legro 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.2019.12.023Palomba S, Santagni S, Falbo A, La Sala GB. Complications and challenges associated with polycystic ovary syndrome: current perspectives. Int J Womens Health. 2015;7:745-763https://doi.org/10.2147/IJWH.S70314World Health Organization. Polycystic Ovary Syndrome. World Health Organization; 2023. Accessed April 21, 2024. https://www.who.int/news-room/fact-sheets/detail/polycystic-ovary-syndromeZhang 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. ResourcesGiagulli 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.12099Jensterle 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-18-0514Latif 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/jcm12020672Papadakis 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. ResourcesBoniface 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.2023.03.006Check 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#xj4y7vzkgKeenan, 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

A new trial tested a new way to give FSH to improve ovarian function in obese women without PCOS who are struggling to conceive. ResourcesBorgert BJ, Bacchus MW, Hernandez AD, Potts SN, Campbell KJ. The availability of gonadotropin therapy from FDA-approved pharmacies for men with hypogonadism and infertility. Sex Med. 2023;11(2):qfad004. Published 2023 Apr 10. doi:10.1093/sexmed/qfad004Kumar TR. Rerouting of follicle-stimulating hormone secretion and gonadal function. Fertil Steril. 2023;119(2):180-183. doi:10.1016/j.fertnstert.2022.12.005Luu TH, Kuhn K, Bradford AP, Wempe MF, Wittenburg L, Johnson RL, Carlson NE, Kumar TR, Polotsky AJ, Effects of Pulsatile IV FSH Treatment on Ovarian Function in Women with Obesity, Fertility and Sterility (2023), doi: https://doi.org/10.1016/j.fertnstert.2023.05.170University of Colorado, Denver. Dysregulation of FSH in Obesity: Functional and Statistical Analysis. ClinicalTrials.gov identifier: NCT02478775. Updated April 7, 2022. Accessed June 12, 2023. https://clinicaltrials.gov/ct2/show/NCT02478775

New study on combining low-dose dexamethasone with letrozole in women with PCOS who failed to ovulate with letrozole alone. This study looked at ovulation, pregnancy, and live birth rates and took place at the Mayo Clinic from 2019 to 2022. ResourcesBarbieri RL and Ehrmann DA. Diagnosis of polycystic ovary syndrome in adults. In: Post T, ed. UpToDate. Waltham, Mass.: UpToDate; 2034. www.uptodate.com. Accessed May 20, 2023.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/NEJMoa1313517Neblett MF 2nd, Baumgarten SC, Babayev SN, Shenoy CC. Ovulation induction with letrozole and dexamethasone in infertile patients with letrozole-resistant polycystic ovary syndrome [published online ahead of print, 2023 May 2]. J Assist Reprod Genet. 2023;10.1007/s10815-023-02817-9. doi:10.1007/s10815-023-02817-9

Women report their use of herbs and supplements to a fertility clinic that assesses their herb-drug interactions.ResourcesFriedman J, Sheeder J, Lazorwitz A, Polotsky AJ. Herbal supplement use among reproductive-aged women in an academic infertility practice. F S Rep. 2022;4(1):104-111. Published 2022 Dec 17. doi:10.1016/j.xfre.2022.12.001Natural Medicines Database Checker. Therapeutic Research Center. Updated 2023. Accessed April 26, 2023. https://naturalmedicines.therapeuticresearch.com

Does vaginal progesterone prevent miscarriages after early pregnancy bleeding? The research world has yet to agree, but a recently published Australian study (aka "the STOP trial") attempted to tackle this question. After seven years of recruiting ~300 women, the STOP trial was stopped prematurely based on early results. Hurdles with study execution plus thinly-disguised jabs at other research made for an interesting paper. Bordewijk EM, Li W, Gurrin LC, Thornton JG, van Wely M, Mol BW. An investigation of seven other publications by the first author of a retracted paper due to doubts about data integrity. Eur J Obstet Gynecol Reprod Biol. 2021;261:236-241. doi:10.1016/j.ejogrb.2021.04.018Carmichael SL, Shaw GM, Laurent C, Croughan MS, Olney RS, Lammer EJ. Maternal progestin intake and risk of hypospadias. Arch Pediatr Adolesc Med. 2005 Oct;159(10):957-62. doi: 10.1001/archpedi.159.10.957. PMID: 16203941.Casarramona G, Lalmahomed T, Lemmen C, et al. The efficacy and safety of luteal phase support with progesterone following ovarian stimulation and intrauterine insemination: A systematic review and meta-analysis. Front Endocrinol (Lausanne). 2022;13:960393. Published 2022 Sep 2. doi:10.3389/fendo.2022.960393 Coomarasamy A, Devall AJ, Cheed V, et al. A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy. N Engl J Med. 2019;380(19):1815-1824. doi:10.1056/NEJMoa1813730. Devall AJ, Papadopoulou A, Podesek M, et al. Progestogens for preventing miscarriage: a network meta-analysis. Cochrane Database Syst Rev. 2021;4(4):CD013792. Published 2021 Apr 19. doi:10.1002/14651858.CD013792.pub2McLindon LA, James G, Beckmann MM, et al. Progesterone for women with threatened miscarriage (STOP trial): a placebo-controlled randomized clinical trial [published online ahead of print, 2023 Feb 20]. Hum Reprod. 2023;dead029. doi:10.1093/humrep/dead029Meurer WJ, Tolles J. Interim Analyses During Group Sequential Clinical Trials. JAMA. 2021;326(15):1524-1525. doi:10.1001/jama.2021.10174Oripro (progesterone pessary used in clinical trial) accessible at https://www.healthdirect.gov.au/medicines/brand/amt,124041000036109/oriproŞükür YE, Göç G, Köse O, et al. The effects of subchorionic hematoma on pregnancy outcome in patients with threatened abortion. J Turk Ger Gynecol Assoc. 2014;15(4):239-242. Published 2014 Dec 1. doi:10.5152/jtgga.2014.14170Yan X, Xu H, Li J, Xu Z, Niu Y, Wang Y. Subchorionic hematoma and risk of preterm delivery: a systematic review and meta-analysis. Am J Obstet Gynecol MFM. 2023;5(1):100791. doi:10.1016/j.ajogmf.2022.100791

This is the first randomized controlled multi-arm trial comparing how three hCG trigger doses impact endogenous progesterone levels in IVF- fresh embryo transfer cycles. ResourcesAbdalla HI, Ah-Moye M, Brinsden P, Howe DL, Okonofua F, Craft I. The effect of the dose of human chorionic gonadotropin and the type of gonadotropin stimulation on oocyte recovery rates in an in vitro fertilization program. Fertil Steril. 1987;48(6):958-963. doi:10.1016/s0015-0282(16)59591-0Pabuçcu E, Pabuçcu R, Gürgan T, Tavmergen E. Luteal phase support in fresh and frozen embryo transfer cycles [published online ahead of print, 2020 Jun 22]. J Gynecol Obstet Hum Reprod. 2020;101838. doi:10.1016/j.jogoh.2020.101838Svenstrup L, Möller S, Fedder J, et al. Does the HCG trigger dose used for IVF impact luteal progesterone concentrations? a randomized controlled trial. Reprod Biomed Online. 2022;45(4):793-804. doi:10.1016/j.rbmo.2022.04.019Vuong LN, Ho TM, Pham TD, Ho VNA, Andersen CY, Humaidan P. The early luteal hormonal profile in IVF patients triggered with hCG. Hum Reprod. 2020;35(1):157-166. doi:10.1093/humrep/dez235

This is the first meta-analysis published in seven years to examine dose-response associations between caffeine or coffee consumption and pregnancy loss.ResourcesBlehar MC, Spong C, Grady C, Goldkind SF, Sahin L, Clayton JA. Enrolling pregnant women: issues in clinical research. Womens Health Issues. 2013;23(1):e39-e45. doi:10.1016/j.whi.2012.10.003Jafari A, Naghshi S, Shahinfar H, et al. Relationship between maternal caffeine and coffee intake and pregnancy loss: A grading of recommendations assessment, development, and evaluation-assessed, dose-response meta-analysis of observational studies. Front Nutr. 2022;9:886224. Published 2022 Aug 9. doi:10.3389/fnut.2022.886224New World Encyclopedia contributors, "Caffeine," New World Encyclopedia, , https://www.newworldencyclopedia.org/p/index.php?title=Caffeine&oldid=794371 (accessed November 27, 2022).Sasaki S, Limpar M, Sata F, Kobayashi S, Kishi R. Interaction between maternal caffeine intake during pregnancy and CYP1A2 C164A polymorphism affects infant birth size in the Hokkaido study. Pediatr Res. 2017;82(1):19-28. doi:10.1038/pr.2017.70White JR Jr, Padowski JM, Zhong Y, et al. Pharmacokinetic analysis and comparison of caffeine administered rapidly or slowly in coffee chilled or hot versus chilled energy drink in healthy young adults. Clin Toxicol (Phila). 2016;54(4):308-312. doi:10.3109/15563650.2016.1146740Yang A, Palmer AA, de Wit H. Genetics of caffeine consumption and responses to caffeine. Psychopharmacology (Berl). 2010;211(3):245-257. doi:10.1007/s00213-010-1900-1

This is the first study to test the use of vaginal tadalafil on endometrial thickness and pregnancies in women using IVF to conceive. ResourcesBalduyck J, Ameye A, Decleer W. Effect of vaginal/oral tadalafil on endometrial thickness in IVF patients: a double-blind, placebo controlled RCT: a pilot study. Facts Views Vis Obgyn. 2022;14(2):155-161. doi:10.52054/FVVO.14.2.026Belapurkar P, Jaiswal A, Madaan S. Comparison of Efficacy Between Vaginal Sildenafil and Granulocyte-Colony Stimulating Factor (G-CSF) in Improving Endometrial Thickness (ET) in Infertile Women. Cureus. 2022;14(6):e26415. Published 2022 Jun 29. doi:10.7759/cureus.26415Cialis. Package Insert. Eli Lilly and Company; 2011.Heger A, Sator M, Walch K, Pietrowski D. Smoking Decreases Endometrial Thickness in IVF/ICSI Patients. Geburtshilfe Frauenheilkd. 2018;78(1):78-82. doi:10.1055/s-0043-123762Mostafa T. Useful Implications of Low-dose Long-term Use of PDE-5 Inhibitors. Sex Med Rev. 2016;4(3):270-284. doi:10.1016/j.sxmr.2015.12.005

A recent randomized controlled trial compares ovarian stimulation protocols (standard vs. tamoxifen vs. letrozole) for freezing oocytes or embryos used in women diagnosed with breast cancer.

A recent well-designed American trial asked women with PCOS and obesity to take either placebo or GLP-1 agonist. 1/3 of participants were African-American and 2/3 were Caucasian. Most women had a goal of pregnancy.After 32 weeks, the women were compared for differences in weight loss, menses, and hormones. Links and study details can be found at www.yourfertilitypharmacist.comThe differences were significant in many ways.

An overview of research on women who completed ICSI, IVF, and/or embryo transfer while actively or recently testing positive for SARS-CoV-2 (COVID-19).

A large multi-national study detects higher stroke risks in women with infertility, miscarriages, and stillbirths.

ResourcesCDC-State-Specific Assisted Reproductive Technology Surveillance. https://www.cdc.gov/art/state-specific-surveillance/index.html Accessed May 20, 2022.Herbenick D, van Anders SM, Brotto LA, Chivers ML, Jawed-Wessel S, Galarza J. Sexual Harassment in the Field of Sexuality Research. Arch Sex Behav. 2019;48(4):997-1006. doi:10.1007/s10508-019-1405-x brilliant paper!Horvath K. Does Bragdon v. Abbott Provide the Missing Link for Infertile Couples Seeking Protection under the ADA?, 2 DePaul J Health Care L. 1999; 819 https://via.library.depaul.edu/jhcl/vol2/iss4/4 Accessed May 20, 2022. Legal background for asserting workplace protection during infertility treatments. Ikemoto Y, Kuroda K, Endo M, et al. Analysis of severe psychological stressors in women during fertility treatment: Japan-Female Employment and Mental health in Assisted reproductive technology (J-FEMA) study. Arch Gynecol Obstet. 2021;304(1):253-261. doi:10.1007/s00404-020-05923-6Imai Y, Endo M, Kuroda K, et al. Risk factors for resignation from work after starting infertility treatment among Japanese women: Japan-Female Employment and Mental health in Assisted reproductive technology (J-FEMA) study [published online ahead of print, 2020 Dec 3]. Occup Environ Med. 2020;78(6):426-432. doi:10.1136/oemed-2020-106745Spiggle T. Workplace Rights for Those Suffering From Infertility. Law blog published May 2015. https://spigglelaw.com/workplace-rights-for-those-suffering-from-infertility/#:~:text=According%20to%20the%20United%20States,the%20employer%20violated%20the%20ADA. Accessed May 20, 2022. Law blog summarizing legal protections for infertility care. Volk H, Hadler M. Work Orientations and Perceived Working Conditions across Countries: Results from the 2015 ISSP Survey. International Journal of Sociology. 2018; 48:2, 103-123, DOI: 10.1080/00207659.2018.1446116Ueda Y, Endo M, Kuroda K, et al. Risk factors for infertility treatment-associated harassment among working women: a Japan-Female Employment and Mental health in assisted reproductive technology (J-FEMA) study [published online ahead of print, 2022 May 13]. Int Arch Occup Environ Health. 2022;10.1007/s00420-022-01872-6. doi:10.1007/s00420-022-01872-6

Letrozole with estrogen, just before progesterone: a thoughtful study on frozen embryo transfer.