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GYNs at the REI gates: unsolvable conundrum or unambiguous opportunity?

Contemporary fertility care has matured from a restricted, special interest in women's health care where success sometimes made magazine covers to a well-honed start-to-finish process with ever-improving success rates and an ever-expanding panoply of treatment options. Innovations in both lab and clinic have been exponential and game changing. The specialty now finds itself in the enviable position of an extensive menu of highly successful treatment options but a complicated set of circumstances of access to these options. Emerging technology such as artificial intelligence could facilitate this transition and improve access. But a key corollary to access and leveraging new technology relates to having a credentialed team to deliver care on scale and maintain best practices and outcomes. The current debate focuses on this Rubik's cube of personnel needs in reproductive endocrinology (REI) and weighs how best to expand access and maintain the culture and spirit of REI. A model to include providers other than REI viz, GYNs or APPs is now front and center. The objective of this Opinion is to define the current context for fertility care and within that context evaluate options and consider what a collaborative model that incorporates a spectrum of non-REI providers including GYNs might look like. Such a model may be feasible (or not) to expand access to care on scale while maintaining high standards and best outcomes.

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Ovarian response in preimplantation genetic testing for myotonic dystrophy type 1.

To evaluate ovarian stimulation response in couples undergoing preimplantation genetic testing (PGT-M) for myotonic dystrophy type 1 (DM1) METHODS: Retrospective, observational, multicentric study. Parameters of ovarian response and PGT-M outcomes were compared according to the DM1-affected patient (female or male). A total of 229 couples underwent at least one controlled ovarian hyperstimulation cycle for the PGT-M procedure. Overall, 678 COS cycles were started, leading to 560 cycles with oocyte retrievals and subsequent PGT-M analysis. At the time of the first PGT-M attempt, affected DM1 females were 1 year older and their serum AMH level was significantly lower than that of the healthy partner of affected DM1 males. After higher starting and total doses of exogenous gonadotropins, the number of mature oocytes was not statistically different between both groups (9 [6-13] vs 9 [6-13] mature oocytes, p=0.73). The FORT index was similar in both groups (35.2% [19.2-52.8] vs 33.3% [19.6-50.0], p=0.09), suggesting that antral follicle responsiveness to FSH is not altered. The live birth rate per fresh embryo transfer was 23.8% in the affected females group and 27.6% for the affected males. After adapted controlled ovarian stimulation protocol and starting dose, a similar response (number of mature oocytes) and sensitivity (FORT index) was observed in DM1 females when compared to healthy partners of DM1 males undergoing PGT-M.

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Impact of SARS-CoV-2 on the male reproductive tract: insights from semen analysis and cryopreservation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus behind the COVID-19 pandemic, affects multiple organs, including the male reproductive system. While viral infections can harm male fertility through cytokine storms, the effects of SARS-CoV-2 on fertility are still unclear. Thus, this study aimed to examine the persistence of viral RNA and inflammatory responses in semen following SARS-CoV-2 infection and the safety of conventional freezing and vitrification techniques. Semen samples from 20 patients were collected 3months post-SARS-CoV-2 infection. Samples underwent freezing and vitrification. Molecular and cellular analysis separated seminal plasma and pellets. Flow cytometry characterized immune cells. Viral RNA was extracted from plasma and sperm, followed by RT-qPCR. Cytometric Bead Array measured cytokine levels. Angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) receptors were detected in both plasma and sperm fractions. Five patients exhibited viral RNA-dependent RNA polymerase, indicating potential persistence. Elevated inflammatory cytokines in plasma implied persistent inflammation affecting sperm vitality. Immune cells associated with viral clearance were identified in semen, correlating with receptor expression and cytokines. Both conventional freezing and vitrification were found safe procedures for preserving male fertility. Our study highlights the impact of SARS-CoV-2 on male reproductive health, emphasizing the persistence of viral entry receptors, potential viral RNA presence, the inflammatory environment, and the involvement of immune populations in the male reproductive tract post-infection. Importantly, we confirm the safety of conventional freezing and vitrification techniques for preserving male fertility in assisted reproductive technology programs amidst the COVID-19 pandemic.

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Uniparental disomy (UPD) exclusion in embryos following Preimplantation Genetic Testing for Structural Rearrangements (PGT-SR).

Uniparental disomy (UPD) is a genetic condition which both copies of a chromosome are inherited from a single parent, potentially leading to imprinting disorders. This study aimed to assess the integration of Short Tandem Repeat (STR) analysis into Preimplantation Genetic Testing for Structural Rearrangements (PGT-SR) to assess UPD risk and its impact on selecting euploid embryos for embryo transfer in couples with chromosomal translocations involving imprinted chromosomes. This study evaluated three couples carrying balanced chromosomal translocations: 45,XX,der(13;14)(q10;q10), 46,XX,t(10;11)(q22;q13), and 45,XY,der(14;15)(q10;q10). STR analysis was performed on trophectoderm (TE) biopsies after Whole Genome Amplification (WGA) after PGT-SR analysis using parental blood samples to assess UPD risk in euploid embryos. Haplotyping was conducted with five to six STR markers specific to each rearranged chromosome to detect UPD in euploid embryos. Of the four embryos analyzed across the three families, two couples had euploid embryos that tested negative for UPD. These embryos were successfully transferred, resulting in the birth of two healthy children. In the third family, the euploid embryo also tested negative for UPD but failed to implant after transfer, resulting in no pregnancy. Despite its rarity, UPD involving imprinted chromosomes poses significant clinical risks, as seen in disorders such as Prader-Willi syndrome and Angelman syndrome. This study highlights the importance of integrating UPD screening into PGT-SR protocols, to detect both heterodisomic and isodisomic UPD events minimizing the risk of severe genetic disorders. Integrating STR-based UPD screening within PGT-SR workflows is a reliable and cost-effective strategy that enhances embryo selection and mitigates the risk of imprinting disorders. This approach improves reproductive outcomes for families with chromosomal rearrangements, offering a practical advancement in assisted reproduction.

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A review of the association between in vitro fertilization and children's neurocognitive development.

This review investigated the current research on the association between in vitro fertilization and children's neurocognitive development. Twenty studies were analyzed, encompassing over 23,000 children conceived through IVF, and compared to those conceived naturally. The findings on overall cognitive function were mixed, as measured by IQ. Some studies showed no significant differences between IVF and naturally conceived children, while others suggested slight variations. There is emerging evidence that IVF might correlate with specific cognitive domains like language and motor skills, although more research is needed. Several established factors, including maternal age, education level, and birth weight, are associated with children's cognitive development, regardless of conception method. Future research should explore how these factors interact with IVF and investigate a broader range of cognitive domains. Socioeconomic background and parental involvement are essential considerations for understanding a child's developmental trajectory. The inconclusive nature of some findings highlights the need for further research with larger sample sizes, more extended follow-up periods, and robust methodologies. This research has potential implications for parents considering IVF or ICSI, healthcare professionals providing guidance, and future efforts to tailor support systems for children conceived through assisted conception techniques. Open communication about the current state of knowledge and responsible communication of research findings is crucial.

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