Katler Q, Verrilli L. Patience and persistence: Is duration the missing piece for treating polycystic ovarian syndrome resistance? Fertil Steril. 2022 Nov 13:S0015-0282(22)02035-0. doi: 10.1016/j.fertnstert.2022.11.008. Epub ahead of print. PMID: 36379262.

This editorial discusses the strengths and weaknesses of an extended letrozole protocol for ovulation induction for patients with refractory PCOS undergoing IVF. The protocol involves extending the standard 5 mg letrozole protocol from 5 to 7 or 10 days, keeping the same letrozole dose, in women who did not respond after the initial 5 days of treatment. The editorial discusses limitations to the study, such as small sample size and the inability to analyze secondary outcomes, and study strengths, such as the potential to reduce financial barriers with this method by reducing the need for ovarian drilling.

Romanski P, Bortoletto P, Malmsten J, Tan KS, Spandorfer S. Pregnancy outcomes after oral and injectable ovulation induction in infertile women with low anti-müllerian hormone level compared to normal anti-müllerian hormone level. Fert Steril. 2022 Nov 12. doi: 10.1016/j.fertnstert.2022.09.010.

This retrospective cohort study was initiated to determine the ongoing pregnancy rate among women diagnosed with infertility with low level of antimullerian hormone level compared to those with normal antimullerian hormone levels after oral and injectable ovulation induction/intrauterine insemination (OI/IUI). A total of 7,169 OI/IUI cycles were included: 3,122 patients completed 5,539 oral antiestrogen cycles and 1,060 women completed 1,630 injectable gonadotropin cycles at a large academic center between 2015 and 2019. Significant findings from the study include: women over the age of 35 and 35-40 years old with low AMH treated with injectable gonadotropins had a significantly reduced ongoing pregnancy rate compared to women of similar age with normal AMH levels. The difference is likely due to an unexpectedly high ongoing pregnancy rate in the normal AMH group. The decline in ongoing pregnancy rate corresponds with a reduction in AMH from 1.0 ng/mL in this cohort of women.

Ávila C, Vinay JI, Arese M, Saso L, Rodrigo R. “Antioxidant Intervention against Male Infertility: Time to Design Novel Strategies”. Biomedicines. 2022 Nov. doi: 10.3390/biomedicines10123058.

Recent findings in research have indicated that reactive oxygen species pathophysiology influences male infertility, but an antioxidant therapy to treat male infertility has yet to be introduced. This review provides an in-depth analysis of the literature regarding antioxidants and oxidative stress as contributors to male infertility and identifies gaps in the current literature. Authors identify a need for therapeutics and interventions that are based on the time course of spermatogenesis and oxidative stress, as well as provide a summary of sources of reactive oxygen species that may contribute to male infertility.

Evans-Hoeker E, Wang Z, Groen H, Cantineau AEP, Thurin-Kjellberg A, Bergh C, Laven JSE, Dietz de Loos A, Jiskoot G, Baillargeon JP, Palomba S, Sim K, Moran LJ, Espinós JJ, Moholdt T, Rothberg AE, Shoupe D, Hoek A, Legro RS, Mol BW, Wang R; Venus-IPD Collaboration. Dietary and/or physical activity interventions in women with overweight or obesity prior to fertility treatment: protocol for a systematic review and individual participant data meta-analysis. BMJ Open. 2022 Nov 7;12(11):e065206. doi: 10.1136/bmjopen-2022-065206. PMID: 36344004; PMCID: PMC9644352.

The Venus-IPD group presents a protocol to establish a meta-analysis to understand the effectiveness and safety of dietary and/or physical activity interventions in overweight or obese women prior to beginning fertility treatments. Data will be gathered from retrospective cohort studies that involved dietary and/or physical activity interventions and compared outcomes from patients who received standard advice concerning healthy lifestyle to patients without intervention. Quasi-RCTs and women who underwent bariatric surgery are to be excluded. Studies will be identified from the following databases: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL). Leading authors from the included studies will receive a list of requested data. The main analysis will be based on the intention-to-treat principle. Results from this study have the potential to advise clinicians on the value of postposing fertility treatment for overweight or obese women to receive dietary and/or physical activity interventions to improve reproductive, maternal, and perinatal outcomes.

Romanello JP, Sun B, Hill MJ, Singer T, O’Brien JE. The impact of the COVID-19 pandemic on gestational carriers. J Assist Reprod Genet. 2022 Oct;39(10):2365-2372. doi: 10.1007/s10815-022-02622-w. Epub 2022 Sep 24. PMID: 36152113; PMCID: PMC9510232.

The COVID-19 pandemic required ART practice centers to reevaluate and adapt their practice processes, having a particularly negative effect on the gestational carrier process. This article provides a comprehensive review of the changes made at the practice level to accommodate the required precautions during the COVID-19 pandemic for couples utilizing a gestational carrier, and gestational carriers themselves. Topics include the added psychological stress unto gestational carriers from the pandemic, changes to the gestational carrier process, patient safety during pregnancy and the pandemic, vaccination counseling, and the new normal in the REI practice.

Awadalla MS, Agarwal R, Ho JR, McGinnis LK, Ahmady A. Effect of trophectoderm biopsy for PGT-A on live birth rate per embryo in good prognosis patients. Arch Gynecol Obstet. 2022 Oct;306(4):1321-1327. doi: 10.1007/s00404-022-06679-x. Epub 2022 Jul 12. PMID: 35821525; PMCID: PMC9470687.

Punjani N, Bortoletto P, Romanski PA, Kashanian J, Spandorfer S. Advancing paternal age does not negatively impact fresh embryo transfer cycle outcomes. Reprod Biomed Online. 2022 Oct;45(4):737-744. doi: 10.1016/j.rbmo.2022.04.014. Epub 2022 Apr 29. PMID: 35840498.

Romanski PA, Bortoletto P, Pfeifer SM, Lindheim SR. An overview and video tutorial to the new interactive website for the American Society for Reproductive Medicine Müllerian Anomalies Classification 2021. Am J Obstet Gynecol. 2022 Oct;227(4):644-647. doi: 10.1016/j.ajog.2022.06.049. Epub 2022 Jun 28. PMID: 35777427. , Bortoletto P, Pfeifer SM, Lindheim SR. An overview and video tutorial to the new interactive website for the American Society for Reproductive Medicine Müllerian Anomalies Classification 2021. Am J Obstet Gynecol. 2022 Oct;227(4):644-647. doi: 10.1016/j.ajog.2022.06.049. Epub 2022 Jun 28. PMID: 35777427.

Siegel DR, Grau L, Sammel M, Nel-Themaaat L, Santoro N, Polotsky AJ. Anti-Müllerian Hormone and Follicle-Stimulating Hormone Are Poor Independent Predictors of Live Birth After Assisted Reproductive Technology. Reprod Sci. 2022 Oct 4. doi: 10.1007/s43032-022-01099-3. Epub ahead of print. PMID: 36194358.

Selter JH, Price TM, Harris BS. Fibroids in pregnancy: a growing or shrinking issue? Fertil Steril. 2022 Oct;118(4):666-667. doi: 10.1016/j.fertnstert.2022.08.001. Epub 2022 Sep 2. PMID: 36064663.

Dilday E, Gigg M, Hoyos L, Quinn M, Markovic D, Kroener L. Luteal phase support with progesterone does not improve pregnancy rates in patients undergoing ovarian stimulation with letrozole. Reprod Biomed Online. 2023 Jan;46(1):123-128. doi: 10.1016/j.rbmo.2022.09.012. Epub 2022 Sep 20. PMID: 36396533.

Supplemental progesterone is routinely used as luteal phase support in non-IVF fertility treatments, despite limited data to support its use. This was a retrospective cohort study that included 273 patients undergoing ovarian stimulation with letrozole paired with IUI or timed intercourse between January 2018 and October 2021. A total of 492 letrozole ovarian cycles were included. Ovulation stimulation protocol included baseline transvaginal ultrasound on cycle day 2 or 3, and letrozole (2.5, 5, or 7.5 mg) daily for five days. When given, vaginal progesterone (Prometrium, 200 mg) was initiated two days post-IUI or 4 days post-hCG trigger in timed intercourse cycles, twice or three times daily. Of these cycles, there was not a significant difference in multifollicular development between those who did and those who did not receive progesterone (P=0.337), as well as no difference in unadjusted clinical pregnancy rate between those who did and those who did not receive progesterone (P=0.645). Live birth rate and infant weight at delivery were similarly not significantly different between groups (P=0.599, 0.076, respectively).

Plowden TC, Mumford SL, Wild RA, Cedars MI, Steiner AZ, Franasiak JM, Diamond MP, Santoro N. Probability of Pregnancy With Mono vs Multiple Folliculogenesis in Women With Unexplained Infertility. J Endocr Soc. 2022 Sep 15;7(1):bvac142. doi: 10.1210/jendso/bvac142. PMID: 36447958; PMCID: PMC9692188.

This study was conducted as a secondary analysis of a randomized controlled trial that included 12 clinical sites across the US. The trial ‘Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation with 3 treatment arms: gonadotropins, clomiphene, or letrozole, combine with intrauterine insemination (AMIGOS trial)’ included women aged 18 to 40 years old with a normal uterine cavity, at least 1 patent fallopian tube, and male partners with ≥5 million total motile sperm. A total of 900 couples were enrolled. In the overall cohort, women with one mature follicle ≥16 mm at the time of hCG trigger were less likely to have a clinical pregnancy (RR, 0.70; 95% CI, 0.54-0.89) and live birth (RR, 0.67; 95% CI, 0.54-0.89) compared to women with ≥2 follicles larger than 16 mm. Comparable outcomes were observed when follicle size cutoff was ≥18 mm; women with one follicle were less likely to have a clinical pregnancy (RR, 0.77; 95% CI, 0.60-0.98) and live birth (RR, 0.75; 95% CI 0.58-0.97). When stratified by treatment modality, women using letrozole saw no difference in chance of live birth and follicle number, while women using clomiphene or gonadotropins were more likely to have a clinical pregnancy and live birth when having ≥2 follicles as opposed to one follicle.

Matevossian K, Rivelli A, Uhler ML. Fertility knowledge and views on egg freezing and family planning among surgical specialty trainees. AJOG Glob Rep. 2022 Sep 7;2(4):100096. doi: 10.1016/j.xagr.2022.100096. PMID: 36536848; PMCID: PMC9758326.

A survey was emailed to medical trainees across a broad range of medical specialties to gather information about US residents’ and fellows’ fertility knowledge and their views on family planning. The responses from those who completed the survey suggest that women physicians and Ob/Gyn trainees do not have greater knowledge of basic female fertility than males or those in other specialties. Female trainees were less likely to be married or have children and more likely to report postponing childbearing.

Romanski PA, Aluko A, Bortoletto P, Elias R, Rosenwaks Z. Age-specific blastocyst conversion rates in embryo cryopreservation cycles. Reprod Biomed Online. 2022 Sep;45(3):432-439. doi: 10.1016/j.rbmo.2022.04.006. Epub 2022 Apr 21. PMID: 35610153.

Romanski PA, Bortoletto P, Pfeifer SM. Cervical agenesis: surgical preservation of reproductive potential in spite of anatomic variation. Fertil Steril. 2022 Sep;118(3):596-597. doi: 10.1016/j.fertnstert.2022.07.004. PMID: 36116805.

Cervical agenesis is a rare anomaly that occurs in 0.001% of the general population, granting even experienced reproductive physicians limited exposure to this congenital disorder. This editorial touches on the historical management, and poor associated outcomes, of the condition. Recent developments have determined that uterovaginal/vestibular anastomosis are the recommended treatment for this condition, but each case should be treated on a case-by-case basis, leading to variable surgical techniques per surgeon. The editorial continues a discussion of a recently developed surgical technique by Fedele et al. (Fertil Steril 2021) utilizing laparoscopically assisted uterovaginal/vestibular anastomosis for patients with cervical agenesis with complete or partial vaginal agenesis.

Hewitt SC, Wu SP, Wang T, Ray M, Brolinson M, Young SL, Spencer TE, DeCherney A, DeMayo FJ. The Estrogen Receptor α Cistrome in Human Endometrium and Epithelial Organoids. Endocrinology. 2022 Sep 1;163(9):bqac116. doi: 10.1210/endocr/bqac116. PMID: 35895287; PMCID: PMC9368022.

Women aged 19 to 34 years old, with regular intermenstrual interval between 25 and 35 days, and no history of infertility or pelvic disease were included in the study. Endometrial biopsies were collected and processed for ESR1 ChIPseq and isolation of epithelial cells for culture of organoids. Study findings include a preferential enrichment of HOX motifs in the mid-secretory ESR1 peaks, and bHLH motifs are enriched in proliferative and mid-secretory ESR1 peaks. Data presented in this study elucidates details of estrogen-mediated response in uterine tissue.

Siegel DR, Sheeder J, Kramer W, Roeca C. Are donor-conceived people willing to use donors themselves? Insights from individuals conceived via donor-assisted reproduction. Hum Reprod. 2022 Aug 25;37(9):2087-2094. doi: 10.1093/humrep/deac169. PMID: 35906918.

Utilizing a web-based survey that was distributed to users of the Sibling Donor Registry, this study found that 40.2% of people who were conceived using donor gametes would consider using donor gametes themselves and 24.6% were undecided. Those who were undecided or had already used donor gametes tended to be younger, and less likely to be married or identify as female than those who would not consider donor gametes.

Martin S, Deng J, Searl T, Ohlander S, Harrington DA, Stupp SI, Dynda D, McVary KT, Podlasek CA. Sonic Hedgehog Signaling in Primary Culture of Human Corpora Cavernosal Tissue From Prostatectomy, Diabetic, and Peyronie’s Patients. J Sex Med. 2022 Aug;19(8):1228-1242. doi: 10.1016/j.jsxm.2022.04.010. Epub 2022 Jun 23. PMID: 35752559; PMCID: PMC9329230.

Akers A, New EP, Plosker S, Silva CP, Sprague R, Imudia AN. Oocyte Retrieval in Asymptomatic Patients Positive for SARS-CoV-2. Case Rep Obstet Gynecol. 2022 Aug 12;2022:3107747. doi: 10.1155/2022/3107747. PMID: 35990707; PMCID: PMC9391171.

COVID-19 has created an additional barrier for women who wish to or are currently undergoing fertility treatment. Fertility centers should address asymptomatic, COVID-19 positive patients on a case-by-case basis in order to ensure safety to center staff and the patient, while also mitigating the dangers associated with cycle cancellation. This study is a discussion of two case studies where women underwent oocyte retrievals and were asymptomatic but tested positive for COVID-19. In both special cases, the risks of canceling the cycles were heavily considered by practice physicians and risk management, and extra precautions were taken to ensure no medical staff were also infected.

Peters BA, Santoro N, Kaplan RC, Qi Q. Spotlight on the Gut Microbiome in Menopause: Current Insights. Int J Womens Health. 2022 Aug 10;14:1059-1072. doi: 10.2147/IJWH.S340491. PMID: 35983178; PMCID: PMC9379122.

This review emphasizes the need to further study the gut microbiome, a key contributor to women’s health, in relation to a woman’s shift into a menopause. Authors include a discussion on the gut microbiome and hormonal transition through pregnancy, pre-menopause, and post-menopause. Particular attention is drawn to the influence of hormones on microbial translocation in the gut barrier, and the role of hormones, specifically estrogens and progesterone, as regulators of the immune system. Additionally, current studies of menopause and the gut microbiome are summarized, as well as the findings. This discussion prompts the need for further research on the influence of the gut microbiome’s ability to recycle sex hormones post-menopause.