Your Fertility Pharmacist: Recent Episodes
Your Fertility Pharmacist—Infertility and Reproductive Medicine, Fertility Medications
The latest fertility research presented by a board-certified clinical pharmacist. For women trying to conceive, this information can help to navigate the science behind the fertility journey.
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).
Resource
Jadva V, Shaw K, Bay B, et al. The experiences of parents with a child born after preimplantation genetic testing. Fertil Steril. 2024;122(4):740-743. doi:10.1016/j.fertnstert.2024.05.141
The most rigorously designed trial of intraovarian PRP (to date) demonstrated no improvements in # of mature oocytes obtained or # of live births versus placebo.
Study BackgroundWHAT
- 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 and modest quality research has shown promising results with PRP for POR
- High-quality study is needed to investigate PRP’s impact for POR with IVF
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
Statistics (Briefly)* 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
Results* 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
Authors’ Thoughts & Conclusions* 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. andKruljac 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
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
Resources
Borgert 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/qfad004
Kumar TR. Rerouting of follicle-stimulating hormone secretion and gonadal function. Fertil Steril. 2023;119(2):180-183. doi:10.1016/j.fertnstert.2022.12.005
Luu 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.2023.05.170
University 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.
Resources
Barbieri 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/NEJMoa1313517
Neblett 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
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.
Resources
Barbieri 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/NEJMoa1313517
Neblett 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.
Resources
Friedman 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.2022.12.001
Natural 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 study was prematurely stopped 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.2021.04.018
Carmichael 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.pub2
McLindon 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/dead029
Meurer WJ, Tolles J. Interim Analyses During Group Sequential Clinical Trials. JAMA. 2021;326(15):1524-1525. doi:10.1001/jama.2021.10174
Oripro (progesterone pessary used in clinical trial) accessible at https://www.healthdirect.gov.au/medicines/brand/amt,124041000036109/oripro
Şükür 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.2014.14170
Yan 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
Resources
Abdalla 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)59591-0
Pabuçcu 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.2020.101838
Svenstrup 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.2022.04.019
Vuong 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.
Resources
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Jafari 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.2022.886224
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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.2017.70
White 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:10.3109/15563650.2016.1146740
Yang 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.
Resources
Balduyck 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.14.2.026
Belapurkar 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.26415
Cialis. 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-0043-123762
Mostafa 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.
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.
Resources
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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/s00404-020-05923-6
Imai 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-2020-106745
Spiggle 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.
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Letrozole with estrogen, just before progesterone: a thoughtful study on frozen embryo transfer.
Resources
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Best D, Avenell A, Bhattacharya S. How effective are weight-loss interventions for improving fertility in women and men who are overweight or obese? A systematic review and meta-analysis of the evidence. Hum Reprod Update. 2017;23(6):681-705. doi:10.1093/humupd/dmx027
Gorgojo-Martínez JJ, Basagoiti-Carreño B, Sanz-Velasco A, Serrano-Moreno C, Almodóvar-Ruiz F. Effectiveness and tolerability of orlistat and liraglutide in patients with obesity in a real-world setting: The XENSOR Study. Int J Clin Pract. 2019;73(11):e13399. doi:10.1111/ijcp.13399
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Practice Committee of the American Society for Reproductive Medicine. Electronic address: asrm@asrm.org. Obesity and reproduction: a committee opinion [published online ahead of print, 2021 Sep 25]. Fertil Steril. 2021;S0015-0282(21)01941-5. doi:10.1016/j.fertnstert.2021.08.018
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Wang Z, Zhao J, Ma X, et al. Effect of Orlistat on Live Birth Rate in Overweight or Obese Women Undergoing IVF-ET: A Randomized Clinical Trial. J Clin Endocrinol Metab. 2021;106(9):e3533-e3545. doi:10.1210/clinem/dgab340
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Barishansky SJ, Shapiro P, Meyman G, Pavone ME, Lawson AK. Reproductive endocrinologists' knowledge and attitudes in the identification of intimate partner violence [published online ahead of print, 2021 Sep 16]. Fertil Steril. 2021;S0015-0282(21)01934-8. doi:10.1016/j.fertnstert.2021.08.011
https://stacks.cdc.gov/view/cdc/60893
Cheng D, Horon IL. Intimate-partner homicide among pregnant and postpartum women. Obstet Gynecol. 2010;115(6):1181-1186. doi:10.1097/AOG.0b013e3181de0194
National Domestic Violence Hotline www.thehotline.org or 1-800-799-SAFE (7233)
Sharifi, F., J. Jamali, M. Larki, and R. L. Roudsari. “Domestic Violence Against Infertile Women : A Systematic Review and Meta-Analysis”. Sultan Qaboos University Medical Journal [SQUMJ], vol. 1, no. 1, June 2021, doi:10.18295/squmj.5.2021.075.
How relevant are a woman's feelings on getting pregnant to her sexual satisfaction? This study attempted to find out.
Resources
Byers ES, MacNeil S. Further validation of the interpersonal exchange model of sexual satisfaction. J Sex Marital Ther. 2006;32(1):53-69. doi:10.1080/00926230500232917
Daniels K, Daugherty J, Jones J. Current contraceptive status among women aged 15-44: United States, 2011-2013. NCHS Data Brief. 2014;(173):1-8.
Johnson, David R. The National Survey of Fertility Barriers, 2010 [United States]. Ann Arbor, MI: Inter-university Consortium for Political and Social Research [distributor], 2017-11-02. https://doi.org/10.3886/ICPSR36902.v1
Shreffler KM, Gibbs L, Tiemeyer S, McQuillan J, Greil AL. Is Reproductive Orientation Associated with Sexual Satisfaction Among Partnered U.S. Women? [published online ahead of print, 2021 Aug 3]. Arch Sex Behav. 2021;10.1007/s10508-021-01984-z. doi:10.1007/s10508-021-01984-z
A July 2021 study compared the differences in GoFundMe campaigns related to infertility based on whether or not the campaign started in a US state that requires healthcare coverage of fertility treatment.
For more details on the research and for other related links, please head to the shownotes at www.yourfertilitypharmacist.com
A recent study looked at the use of Enbrel (etanercept) in women with multiple failed attempts to transfer good quality IVF embryos. This is the largest study to date that has looked at using Enbrel in women with recurrent implantation failure; the results were quite promising.
More details found in the shownotes at www.yourfertilitypharmacist.com
The first study to look at what happens when a physician talks about uncertainty with infertile couples during assisted reproductive technology (ART) consultations.
More details and a link to this fertility research are available in the shownotes at www.yourfertilitypharmacist.com
This episode is about the Iranian research paper called “Resilience as the predictor of quality of life in the infertile couples as the most neglected and silent minorities.” This research was published online in November 2020 in the Journal of Reproductive and Infant Psychology.
Beyond the research, this episode provides historical context of the roles of Iranian wives and examines how that context might impact the research results.
More details and links to the studies mentioned in this episode can be found at www.yourfertilitypharmacist.com
The 20th podcast episode of “Your Fertility Pharmacist” is a bit different. With guest speaker Melsa Maher, fertility acupuncturist, this episode places a special focus on traditional medicine. The audio was recorded over Zoom.
Traditionally, letrozole has been taken for five days in IUI. What happens if, instead, those five days of letrozole are taken all at once?
For additional study details, please head to www.yourfertilitypharmacist.com
The podcast brings up key points of the study. Scientific details and links are in the show notes at www.yourfertilitypharmacist.com
This pioneering study is the first to focus on how adults, raised by lesbian moms, feel about their sperm donors. Study originally published on July 4, 2020 in the journal Fertility and Sterility.
A new Harvard-affiliated study explores whether intramuscular progesterone or vaginal gel progesterone (Crinone 8%) more effectively leads to live births after single frozen embryo transfer. Will their results change IVF practices in the U.S.A.?
A newly published study found that fathers from reproductive assistance (IVF or ICSI) had higher IQ scores than fathers who naturally conceived. This podcast discusses the flaws in the study.
More at www.yourfertilitypharmacist.com
This podcast episode summarizes the study. For even more study details, head to www.yourfertilitypharmacist.com.
This is the first study to look at how socioeconomic factors play into women’s awareness about ectopic pregnancies. Since ectopic pregnancy is still the leading cause of maternal death in early pregnancy, ALL potentially pregnant women need to be able to recognize the seriousness of an ectopic pregnancy and how to access care
A 7 year old girl underwent hormone therapy and surgery to have a chance at fertility. Here were the outcomes from her two egg freezing cycles.
Some of the questions on the questionnaire included: smoking and drinking habits, self-rated physical fitness, self-rated health, socioeconomic factors (education and occupation), diseases, previous diagnosis of depression, and erectile dysfunction.
To learn what differences in stress were found in men with more and less fertility, check out the full show notes on www.yourfertilitypharmacist.com
This study followed three women who were 28, 38, and 32 years old. All three had sought reproductive assistance (ART) and could produce a low quantity of oocytes. The quality of their eggs was low and none could produce a viable embryo. After two key interventions, all three women made top quality embryos and two had babies!
A few months ago, a study was published in Fertility and Sterility that looked at whether or not there is an association between how a baby was conceived and the impact this mode of conception has on serious infections through childhood. This episode reviews the results and what they may mean for women using fertility treatments to conceive.
Today's episode gives a quick summary of ASRM's updated Coronavirus Fertility Treatment Recommendations plus reveals what happened to seven COVID-infected pregnant women at a large New York City hospital.
This episode centers around the drugs being used experimentally to treat COVID-19 and what we know about how these drugs impact pregnant women. The links to the studies and drug information discussed on this episode can be found at “yourfertilitypharmacist.com.”
Before delving into the drugs, let’s touch base on the limited information we have on how pregnant women are impacted by coronavirus, which is the virus manifesting as the respiratory illness called “COVID-19.”The good news is, there have not been any confirmed cases of mothers transferring coronavirus to the baby in utero. Having said that, the limited information we have about delivery outcomes is concerning. A recent article in the Journal of Infection detailed the delivery outcomes from thirteen Chinese women who were pregnant and tested + for coronavirus. They ranged in age from 22 to 36 years old. They had no other pre-existing health conditions. Two women were in their second trimesters, and the other 11 were in their third trimesters. Six of the eleven women who were in their third trimester went into early labor related to fetal distress, premature membrane rupture, and even one stillbirth. The two women who were in their second trimesters did NOT go into early labor or have any other fetal consequences noted – I really hope that the researchers keep close tabs on those two pregnancies so we can learn more information on the impact of second trimester coronavirus infections. Since a lot of these pregnancies had complications, having a treatment for COVID-19 could improve the health of infected mothers and babies.
Regarding medications to treat COVID-19, there are a few drugs that seem promising for an illness that doesn’t yet officially have a cure.
A drug that’s been receiving a TON of press lately is chloroquine, as reports from China and France suggest that it’s effective against COVID-19. Chloroquine was originally approved by the FDA in 1949 to treat malaria, and it was later approved to treat lupus and rheumatoid arthritis. Since chloroquine has been used and tested for so many decades, we have information on how this drug impacts pregnant women and their babies. Chloroquine does go through the placenta and into breastmilk; in mice and monkey babies, this crossing led to vision problems and blindness. These eye problems were not seen in human studies conducted a decade ago in Thailand and in New Guinea on pregnant moms requiring malaria prophylaxis. Thus, the reference book Drugs in Pregnancy and Lactation considers chloroquine to be the unlikely cause of birth defects in humans. It also states that the benefits of preventing and treating malaria outweigh the risks. This permission could potentially be extrapolated to treatment of COVID-19… but before getting too gung-ho about stockpiling chloroquine, a more promising sister drug to chloroquine should be considered.
Hydroxychloroquine is chloroquine with a slightly different molecular structure that makes it less toxic yet just as effective as chloroquine for malaria and for immune-mediated disorders. It was FDA approved in 1955 and also goes by the brand name Plaquenil. Scientists, and therefore the mainstream media, have gotten very excited about using this drug because of a small study from southern France on treating coronavirus. In this study, 14 infected patients received hydroxychloroquine alone, 6 patients received hydroxychloroquine plus an antibiotic called azithromycin, and 16 patients, serving as the control group, who didn’t get hydroxychloroquine at all. After six days, the virus was cleared from the system of all six patients taking both hydroxychloroquine and azithromycin, from 8 out of 14 patients taking hydroxychloroquine alone, and from just two of the sixteen patients who didn’t receive hydroxychloroquine. Those encouraging results were only published five days ago. Since then, hoarding of the medication has become a national issue. It’s such an issue that the FDA is permitting a factory in India that was recently cited for quality issues to ramp up supply of hydroxychloroquine to import to the U.S.
This study inspiring the hydroxychloroquine shortage specifically excluded pregnant women. Given that it is safe to use in pregnancy in other conditions, plus it is generally considered to be a safer drug than chloroquine, it would be reasonable to assume that it would be safe in pregnant women infected with COVID-19. Of the drugs being tested to treat COVID-19, hydroxychloroquine is the drug I feel most confident endorsing for safety and efficacy in pregnant women at this time. I’d also recommend taking it with azithromycin to increase chances of clearing the virus.
Though I’ve given my endorsement, I would be remiss as a pharmacist if I didn’t discuss another promising drug that’s gotten a lot of attention lately. It’s an antiviral called remdesivir, which is NOT officially FDA approved for any illness in the U.S. It is allowed for “compassionate use,” meaning that a patient may be able to gain access to the drug if in a life-threatening condition and there isn’t a good alternative treatment available. The manufacturer of this drug has seen such a surge in requests to use remdesivir during this pandemic that they just cut off new requests to use this drug EXCEPT for pregnant women and in children.
So, while it remains available for pregnant women, is it actually safe and effective? In 2018/2019, remdesivir was given to six pregnant Congolese women infected with Ebola who were enrolled in a clinical trial looking at four investigational drugs to potentially treat that illness.
This trial was published in Dec 2019 in the New England Journal of Medicine; unfortunately, after looking over the study and all of the published information, there is very little detail on how these six pregnant women responded to remdesivir. We don’t know their ages, how far along they were in their pregnancies, etc. One reason that the trial may have given so little focus to so few pregnant women taking remdesivir is because two other drugs in the study were found to be more effective at treating Ebola, so they stopped giving remdesivir in favor of other drugs. I gleaned the study for details and read in the supplementary index about the adverse events broken down by patient and drug. One of the other experimental drugs mentioned one baby born with hydrocephalus and one with a shortened umbilical cord. Because these adverse outcomes were mentioned in a drug that was NOT remdesivir, can we assume that remdesivir does not cause fetal harm?
We still have too little information - six pregnant women taking a drug is simply not enough to draw useful conclusions. In the short-term, we will have to look at press releases for pregnant women who took remdesivir through compassionate use. According to upcoming U.S. studies listed on clinicaltrials.gov, only one of the three remdesivir trials is specifically excluding pregnant women from participating, so hopefully we will have some concrete data once the two inclusive trials have ended. To see the studies included in this podcast, please check out “yourfertilitypharmacist.com.”
Today’s episode centers around the impact on fertility treatments due to coronavirus, which is the virus manifesting as the respiratory illness called “COVID-19.”
On St. Patrick’s Day, the American Society for Reproductive Medicine (for short known as ASRM) released recommendations for managing fertility treatments during the pandemic. These recommendations came from the evidence we currently have on COVID-19. ASRM will update their position by March 30th or earlier as more information comes in. The link to the recommendations is available on my website, “yourfertilitypharmacist.com”
After listing their major recommendations from the eight-page document, I’ll go over the rationale for these momentous statements.
1, no more new treatment cycles for the foreseeable future. By new treatments, they explicitly call out ovulation induction, in vitro-fertilization – including retrievals and frozen embryo transfers, intra-uterine inseminations, and non-urgent gamete cryopreservation.
2, in quotes, is “consider cancellation of all embryo transfers whether fresh or frozen.”
3, keep caring for a patient is already “in cycle” or requires urgent stimulation for cryopreservation. Now, caring for is a gray area, which I will come back to later in this episode.
4 stop any non-urgent diagnostic procedures and elective surgeries.
And the last one, #5, minimize in-person interactions in favor of telehealth.
These recommendations are… extreme, but not shocking, given the surreal times that we are now living in. ASRM laid out how COVID-19 is more contagious and kills 10-15 times more people compared to the flu. There is a scary shortage of personal protective equipment for healthcare workers, so there is a suggestion that the gloves, masks, and other personal protective equipment used by the staff at fertility clinics could be rerouted to healthcare systems directly addressing COVID-19. Since the U.S. is severely deficient in testing and screening capabilities for coronavirus, staff at reproductive centers could unknowingly come into contact with the infection; if reproductive staff come down with the illness, this could easily impair the quality of care needed to treat patients. Most importantly, we still don’t know how COVID-19 infection will impact pregnant women; it’s unclear if a mother can directly pass the virus onto a baby in utero. A recent publication discussed the outcomes of nine pregnant Chinese women who tested positive and showed symptoms for COVID-19. Six out of ten babies born to these COVID-19 infected moms experienced intrauterine fetal distress and met criteria for critical illness. (More details about this publication from China can be found on the study link located on this episode’s webpage).
With the concern for negative impact to babies, women, and healthcare staff, ASRM’s recommendations to stop any non-urgent fertility treatments makes sense. I live in an area where coronavirus has really taken hold, and I’m seeing the uptake of the ASRM recommendations vary based on the local reproductive clinic. Deciding what is urgent and what is not is such a gray area. While a couple of sites haven’t seemed to alter their practices significantly, others are going on a case-by-case basis on whether or not to proceed with a stim cycle or transfer. Many women are feeling heartache over having to delay treatment in the face of a ticking biological clock. Other women are nervous that their cycle will be cancelled at the last-minute as more restrictions come into play. My advice to any active patients at a reproductive clinic would be to touch base with your clinic to know their stance on treatment during this pandemic and how they personally plan to attend to your case. For women who may have the possibility of conceiving naturally, please practice social distancing and keep taking your prenatal vitamins!
That’s the end of today’s episode of “Your Fertility Pharmacist.” In the next episode, I’ll discuss the medications being used experimentally to treat COVID-19 and what we know about how they impact pregnancy. All related links discussed in these episodes will be posted on the website “yourfertilitypharmacist.com.”
Despite the many advancements in science and technology that have been game-changers in the fertility field, there is still so much that is unknown. Even now, roughly 30% of couples seeking reproductive assistance have unexplained fertility. It’s extremely frustrating to not know why you can’t conceive, so I’m thankful to the lady scientists behind this week’s fertility article who posed some good questions. These questions were, how long lasting are the effects of the levonorgestrel IUD after its removed, and how does this IUD impact the future fertility of women who’ve never before had a baby?
Hello, this is “Your Fertility Pharmacist.” This podcast is for women who are trying to overcome infertility. If you keep a pulse on late-breaking fertility research, it could positively alter the course of your fertility journey, as it has for me.
This week’s article was written by Erin Dinehart, Ruth B. Lathi, and Lusine Aghajanova. It was published in the Journal of Assisted Reproduction and Genetics in November 2019.
The Mirena was the first levonorgestrel IUD approved in the U.S. in late 2000. Since then, other levonor IUDs have come out, including Liletta, Skyla, and Kyleena. They all look and act essentially the same. These IUDs will send out a low-level of progesterone, which will make the uterine lining thicken in the cervix. Kind of like a super stuffed up nose in which nothing seems to go in or out easily, the cervix is so plugged up with mucus from this IUD that the sperm can’t easily swim around. Beyond doing its job as a Sperm Stopper, the levonorgestrel IUD also can impact ovulation for up to one year after insertion.
Research has shown that the levonor IUD’s impact on fertility is reversible, BUT there are questions on how quickly fertility returns and to what extent. A 1992 study spent almost two years tracking 140 women who had used a Levonor IUD for an average of 19 months. After the IUD was removed, the pregnancy rates after twelve months of trying were 75.4%, which is lower than the general population, which is 85-92%. Moreover, the 1992 study combined women who had already conceived with women who had never conceived, which makes it harder to tease out the results for women who were trying to have their first baby. A more recent study from 2017 showed similar results - after removing the IUD, 71.2% of women conceived within twelve months. This 2017 study also lumped together the women who had previously given birth with women who hadn’t. So, we still don’t really know how levonor IUDs impacts women who have never had children before and/or women who used the IUD for closer to five years, which is how long Mirena and Kyleena can safely stay inserted.
I just searched clinicaltrials.gov to see if any new studies will be coming out soon with answers to these questions. There were 144 clinical trials related to levonorgestrel intrauterine devices, and NONE of the trials are studying the impact on fertility in women who would be first-time moms. There were studies looking at the satisfaction of women using levonor IUDs, but these studies were also limited to twelve months after IUD insertion.
To conclude, it’s possible that the IUD has a lasting impact on the tissue of the endometrium even after being removed, which may impact fertility. It’s also possible that the IUD impacts fertility differently for women who have already conceived vs. women who have never conceived. We don’t know, so I’m glad that the scientists publicly posed these questions.
I wish I had thought to look into the potential long-term consequences on my fertility before signing up for five years of the Mirena. If I was going to repeat getting an IUD now, I would probably select one that is indicated for three years, given that the data is more closely comparable to three-years vs. five or six years of keeping a levonor IUD in.
The study was published in February 2020 in Reproductive Physiology and Disease, and a link to learn more about the study will be posted on the podcast’s website, www.yourfertilitypharmacist.com.
There was a lot to like about this study. It focused on low ovarian reserve, which is also sometimes called “poor ovarian reserve” or “diminished ovarian reserve.” In pre-menopausal women, this means having a lower quantity or lower quality of eggs that could be used to conceive a baby. Some women can still conceive with these eggs, though it often takes fertility treatments to help make this happen. Results from using this particular PRP treatment are discussed in this episode.