45 research outputs found

    Incorporating patient preference into the management of infertility in women with polycystic ovary syndrome

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    Polycystic ovary syndrome (PCOS) is a heterogeneous condition characterized by anovulation, hyperandrogenism, and polycystic ovaries. Because of the heterogeneous nature of PCOS, women affected by the condition often require a customized approach for ovulation induction when trying to conceive. Treating symptoms of PCOS in overweight and obese women should always incorporate lifestyle changes with the goal of weight-loss, as many women with PCOS will ovulate after losing 5%–10% of their body weight. On the other hand, other factors must be considered including the woman’s age, age-related decline in fertility, and previous treatments she may have already tried. Fortunately, multiple options for ovulation induction exist for women with PCOS. This paper reviews specific ovulation induction options available for women with PCOS, the benefits and efficacy of these options, and the related side effects and risks women can anticipate with the various options that may affect treatment adherence. The paper also reviews the recommended evidence-based strategies for treating PCOS-related infertility that allow for incorporation of the patient’s preference. Finally, it briefly reviews emerging data and ongoing studies regarding newer agents that have shown great promise as first-line agents for the treatment of infertility in women with PCOS

    Association of state insurance mandates for fertility treatment with multiple embryo transfer after preimplantation genetic testing for aneuploidy

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    IMPORTANCE: Multiple gestation is one of the biggest risks after in vitro fertilization (IVF), largely due to multiple embryo transfer (MET). Single embryo transfer (SET) uptake has increased over time and has been attributed to various factors, such as mandated insurance coverage for IVF and preimplantation genetic testing for aneuploidy (PGT-A). OBJECTIVE: To investigate whether mandates for IVF insurance coverage are associated with decreased use of MET after PGT-A. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted using data on embryo transfers reported to the Society for Assisted Reproductive Technology between 2014 and 2016. Data were analyzed from January to October 2021. EXPOSURES: State-mandated coverage for fertility treatment and type of cycle transfer performed (PGT-A, untested fresh, and untested frozen). MAIN OUTCOMES AND MEASURES: Use of MET compared with SET, live birth, and live birth of multiples. RESULTS: There were 110 843 embryo transfers (mean [SD] patient age, 34.0 [4.5] years; 5520 individuals identified as African American [5.0%], 10 035 as Asian [9.0%], 5425 as Hispanic [4.9%], 45 561 as White [41.1%], and 44 302 as other or unknown race or ethnicity [40.0%]); 17 650 transfers used embryos that underwent PGT-A. Overall, among transferred embryos that had PGT-A, there were 9712 live births (55.0%). The odds of live birth were 70% higher with MET vs SET after frozen embryo transfer with PGT-A (OR, 1.70; 95% CI, 1.61-1.78), but the risk of multiples was 5 times higher (OR, 5.33; 95% CI, 5.22-5.44). The odds of MET in cycles with PGT-A in states with insurance mandates were 24% lower than in states without mandates (OR, 0.76; 95% CI, 0.68-0.85). CONCLUSIONS AND RELEVANCE: This study found that despite the promise of using SET with PGT-A, MET after PGT-A was not uncommon. This practice was more common in states without insurance mandates and was associated with a high risk of multiples

    A retrospective cross-sectional study: Fresh cycle endometrial thickness is a sensitive predictor of inadequate endometrial thickness in frozen embryo transfer cycles

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    BACKGROUND: The purpose of this study is to assess predictors of inadequate endometrial cavity thickness (ECT), defined as < 8 mm, in frozen embryo transfer (FET) cycles. METHODS: This is a retrospective cross-sectional study at an academic fertility center including 274 women who underwent their first endometrial preparation with estradiol for autologous FET in our center from 2001-2009. Multivariable logistic regression was performed to determine predictors of inadequate endometrial development in FET cycles. RESULTS: Neither age nor duration of estrogen supplementation were associated with FET endometrial thickness. Lower body mass index, nulliparity, previous operative hysteroscopy and thinner fresh cycle endometrial lining were associated with inadequate endometrial thickness in FET cycles. A maximum thickness of 11.5 mm in a fresh cycle was 80% sensitive and 70% specific for inadequate frozen cycle thickness. CONCLUSIONS: Previous fresh cycle endometrial cavity thickness is associated with subsequent FET cycle endometrial cavity thickness. Women with a fresh cycle thickness of 11.5 mm or less may require additional intervention to achieve adequate endometrial thickness in preparation for a frozen cycle

    A role for Malignant Brain Tumor Domain-containing Protein 1 in human endometrial stromal cell decidualization

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    Up to 30% of women experience early miscarriage due to impaired decidualization. For implantation to occur, the uterine endometrial stromal fibroblast-like cells must differentiate into decidual cells, but the genes required for decidualization have not been fully defined. Here, we show that Malignant Brain Tumor Domain-containing Protein 1 (MBTD1), a member of the polycomb group protein family, is critical for human endometrial stromal cell (HESC) decidualization. MBTD1 predominantly localized to HESCs during the secretory phase and the levels were significantly elevated durin

    Variability in the practice of fertility preservation for patients with cancer

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    Fertility is important to women and men with cancer. While options for fertility preservation (FP) are available, knowledge regarding the medical application of FP is lacking. Therefore we examined FP practices for cancer patients among reproductive endocrinologists (REs). A 36 item survey was sent to board-certified REs. 98% of respondents reported counseling women with cancer about FP options. Oocyte and embryo cryopreservation were universally offered by these providers, but variability was noted in reported management of these cases-particularly for women with breast cancer. 86% of the respondents reported using letrozole during controlled ovarian stimulation (COS) in patients with estrogen receptor positive (ER+) breast cancer to minimize patient exposure to estrogen. 49% of respondents who reported using letrozole in COS for patients with ER+ breast cancer reported that they would also use letrozole in COS for women with ER negative breast cancer. Variability was also noted in the management of FP for men with cancer. 83% of participants reported counseling men about sperm banking with 22% recommending against banking for men previously exposed to chemotherapy. Overall, 79% of respondents reported knowledge of American Society for Clinical Oncology FP guidelines-knowledge that was associated with providers offering gonadal tissue cryopreservation (RR 1.82, 95% CI 1.14-2.90). These findings demonstrate that RE management of FP in cancer patients varies. Although some variability may be dictated by local resources, standardization of FP practices and communication with treating oncologists may help ensure consistent recommendations and outcomes for patients seeking FP

    A GREB1-steroid receptor feedforward mechanism governs differential GREB1 action in endometrial function and endometriosis

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    Cellular responses to the steroid hormones, estrogen (E2), and progesterone (P4) are governed by their cognate receptor\u27s transcriptional output. However, the feed-forward mechanisms that shape cell-type-specific transcriptional fulcrums for steroid receptors are unidentified. Herein, we found that a common feed-forward mechanism between GREB1 and steroid receptors regulates the differential effect of GREB1 on steroid hormones in a physiological or pathological context. In physiological (receptive) endometrium, GREB1 controls P4-responses in uterine stroma, affecting endometrial receptivity and decidualization, while not affecting E2-mediated epithelial proliferation. Of mechanism, progesterone-induced GREB1 physically interacts with the progesterone receptor, acting as a cofactor in a positive feedback mechanism to regulate P4-responsive genes. Conversely, in endometrial pathology (endometriosis), E2-induced GREB1 modulates E2-dependent gene expression to promote the growth of endometriotic lesions in mice. This differential action of GREB1 exerted by a common feed-forward mechanism with steroid receptors advances our understanding of mechanisms that underlie cell- and tissue-specific steroid hormone actions

    Mouse models of preterm birth: Suggested assessment and reporting guidelines

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    Preterm birth affects approximately 1 out of every 10 births in the United States, leading to high rates of mortality and long-term negative health consequences. To investigate the mechanisms leading to preterm birth so as to develop prevention strategies, researchers have developed numerous mouse models of preterm birth. However, the lack of standard definitions for preterm birth in mice limits our field\u27s ability to compare models and make inferences about preterm birth in humans. In this review, we discuss numerous mouse preterm birth models, propose guidelines for experiments and reporting, and suggest markers that can be used to assess whether pups are premature or mature. We argue that adoption of these recommendations will enhance the utility of mice as models for preterm birth

    A de novo paradigm for male infertility

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    Funding Information: (DFG, CRU326) to C.F. and F.T. This project was also supported in part by funding from the Australian National Health and Medical Research Council (APP1120356) to M.K.O.B., by grants from the National Institutes of Health of the United States of America (R01HD078641 to D.F.C. and K.I.A., P50HD096723 to D.F.C.) and from the Biotechnology and Biological Sciences Research Council (BB/S008039/1) to D.J.E. Funding Information: We are grateful for the participation of all patients and their parents in this study. We thank Laurens van de Wiel (Radboudumc), Sebastian Judd-Mole (Monash University), Arron Scott and Bryan Hepworth (Newcastle University) for technical support, and Margot J Wyrwoll (University of MĂŒnster) for help with handling MERGE samples and data. This project was funded by The Netherlands Organization for Scientific Research (918-15-667) to J.A.V. as well as an Investigator Award in Science from the Wellcome Trust (209451) to J.A.V. a grant from the Catherine van Tussenbroek Foundation to M.S.O. a grant from MERCK to R.S. a UUKi Rutherford Fund Fellowship awarded to B.J.H. and the German Research Foundation Clinical Research Unit “Male Germ Cells” Publisher Copyright: © 2022, The Author(s).De novo mutations are known to play a prominent role in sporadic disorders with reduced fitness. We hypothesize that de novo mutations play an important role in severe male infertility and explain a portion of the genetic causes of this understudied disorder. To test this hypothesis, we utilize trio-based exome sequencing in a cohort of 185 infertile males and their unaffected parents. Following a systematic analysis, 29 of 145 rare (MAF < 0.1%) protein-altering de novo mutations are classified as possibly causative of the male infertility phenotype. We observed a significant enrichment of loss-of-function de novo mutations in loss-of-function-intolerant genes (p-value = 1.00 × 10−5) in infertile men compared to controls. Additionally, we detected a significant increase in predicted pathogenic de novo missense mutations affecting missense-intolerant genes (p-value = 5.01 × 10−4) in contrast to predicted benign de novo mutations. One gene we identify, RBM5, is an essential regulator of male germ cell pre-mRNA splicing and has been previously implicated in male infertility in mice. In a follow-up study, 6 rare pathogenic missense mutations affecting this gene are observed in a cohort of 2,506 infertile patients, whilst we find no such mutations in a cohort of 5,784 fertile men (p-value = 0.03). Our results provide evidence for the role of de novo mutations in severe male infertility and point to new candidate genes affecting fertility.publishersversionpublishe
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