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Reproductive success relies on proper establishment and maintenance of biological sex. In many animals, including mammals, the primary gonad is initially ovary biased. We previously showed the RNA binding protein (RNAbp), Rbpms2, is required for ovary fate in zebrafish. Here, we identified Rbpms2 targets in oocytes (Rbpms2-bound oocyte RNAs; rboRNAs). We identify Rbpms2 as a translational regulator of rboRNAs, which include testis factors and ribosome biogenesis factors. Further, genetic analyses indicate that Rbpms2 promotes nucleolar amplification via the mTorc1 signaling pathway, specifically through the mTorc1-activating Gap activity towards Rags 2 (Gator2) component, Missing oocyte (Mios). Cumulatively, our findings indicate that early gonocytes are in a dual poised, bipotential state in which Rbpms2 acts as a binary fate-switch. Specifically, Rbpms2 represses testis factors and promotes oocyte factors to promote oocyte progression through an essential Gator2-mediated checkpoint, thereby integrating regulation of sexual differentiation factors and nutritional availability pathways in zebrafish oogenesis.
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Oocitos , Oogénesis , Proteínas de Unión al ARN , Proteínas de Pez Cebra , Pez Cebra , Animales , Femenino , Masculino , Regulación del Desarrollo de la Expresión Génica , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/genética , Nutrientes/metabolismo , Oocitos/metabolismo , Oogénesis/genética , Ovario/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Transducción de Señal , Testículo/metabolismo , Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Proteínas de Pez Cebra/genética , Proteínas de Complejo Poro Nuclear/genética , Proteínas de Complejo Poro Nuclear/metabolismoRESUMEN
Purpose: Transgender and gender diverse (TGD) individuals continue to face adversity, stigma, and inequality, especially in health care. This study aimed to characterize the experience of TGD people and partners of TGD people with regard to fertility treatment. Methods: All TGD patients presenting to a single academic center between 2013 and 2021 were included. Baseline demographics collected included patient age, body mass index, anti-Mullerian hormone, basal antral follicle count, history of gender-affirming surgery, and/or gender-affirming hormone therapy. Outcomes included total patients who progressed to treatment, cycle type(s), and clinical outcomes. Results: In total, 82 patients who identified as TGD or had a partner who identified as TGD presented to care seeking fertility treatment. Of the 141 planned cycles, 106 (75.2%) progressed to treatment. Of the 15 in vitro fertilization (IVF) and co-IVF cycles, 12 achieved live birth. Of the 76 intrauterine inseminations 7 patients were discharged with ongoing pregnancies and one achieved live birth. Conclusion: These findings reaffirm that TGD individuals utilize the entire array of fertility services. With recent advances in access to care and modern medicine, assisted reproductive technology treatment has the power to support TGD patients in building contemporary family structures.
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Reproductive success relies on proper establishment and maintenance of biological sex. In many animals, including mammals, the primary gonad is initially ovary in character. We previously showed the RNA binding protein (RNAbp), Rbpms2, is required for ovary fate in zebrafish. Here, we identified Rbpms2 targets in oocytes (Rbpms2-bound oocyte RNAs; rboRNAs). We identify Rbpms2 as a translational regulator of rboRNAs, which include testis factors and ribosome biogenesis factors. Further, genetic analyses indicate that Rbpms2 promotes nucleolar amplification via the mTorc1 signaling pathway, specifically through the mTorc1-activating Gap activity towards Rags 2 (Gator2) component, Missing oocyte (Mios). Cumulatively, our findings indicate that early gonocytes are in a dual poised, bipotential state in which Rbpms2 acts as a binary fate-switch. Specifically, Rbpms2 represses testis factors and promotes oocyte factors to promote oocyte progression through an essential Gator2-mediated checkpoint, thereby integrating regulation of sexual differentiation factors and nutritional availability pathways in zebrafish oogenesis.
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OBJECTIVE: To assess whether open and minimally invasive myomectomy are associated with changes in postoperative ovarian reserve as measured by serum anti-müllerian hormone (AMH) level. METHODS: This prospective cohort study included patients who were undergoing open abdominal myomectomy that used a tourniquet or minimally invasive (robot-assisted or laparoscopic) myomectomy that used vasopressin. Serum AMH levels were collected before the procedure and at 2 weeks, 3 months, and 6 months after surgery. The mean change in AMH level at each postsurgery timepoint was compared with baseline. The effect of surgical route on the change in AMH level at each timepoint was assessed by using multivariable linear regression. A subanalysis evaluated postoperative changes in AMH levels among the open myomectomy and minimally invasive myomectomy groups individually. RESULTS: The study included 111 patients (mean age 37.9±4.7 years), of whom 65 underwent open myomectomy and 46 underwent minimally invasive myomectomy. Eighty-seven patients contributed follow-up data. Serum AMH levels declined significantly at 2 weeks postsurgery (mean change -0.30 ng/mL, 95% CI -0.48 to -0.120 ng/mL, P=.002). No difference was observed at 3 months or 6 months postsurgery. On multiple linear regression, open myomectomy was significantly associated with a decline in AMH level at 2 weeks postsurgery (open myomectomy vs minimally invasive myomectomy: ß=-0.63±0.22 ng/mL, P=.007) but not at 3 months or 6 months. Subanalysis revealed a significant decline in mean serum AMH levels in the open myomectomy group at 2 weeks (mean change -0.46 ng/mL, 95% CI -0.69 to -0.25 ng/mL, P<.001) postsurgery but not at three or 6 months. In the minimally invasive myomectomy group, no significant differences in mean AMH levels were detected between baseline and any postoperative timepoint. CONCLUSION: Myomectomy is associated with a transient decline in AMH levels in the immediate postoperative period, particularly after open surgery in which a tourniquet is used. Anti-müllerian hormone levels returned to baseline by 3 months after surgery, indicating that myomectomy is not associated with a long-term effect on ovarian reserve, even with the use of a tourniquet to decrease blood loss. FUNDING SOURCE: This study was funded in part by a Roche Diagnostics Investigator-Initiated Study Grant.
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Reserva Ovárica , Miomectomía Uterina , Humanos , Femenino , Adulto , Hormona Antimülleriana , Estudios Prospectivos , Modelos LinealesRESUMEN
OBJECTIVE: To assess whether coronavirus disease 2019 (COVID-19) mRNA vaccination is associated with controlled ovarian hyperstimulation or early pregnancy outcomes. METHODS: This retrospective cohort study included patients who underwent controlled ovarian hyperstimulation or single euploid frozen-thawed embryo transfer at a single academic center. Patients fully vaccinated with a COVID-19 mRNA vaccine were compared with unvaccinated patients who cycled during the same time period. The primary outcome was the fertilization rate for controlled ovarian hyperstimulation and the clinical pregnancy rate for frozen-thawed embryo transfer. Secondary outcomes for controlled ovarian hyperstimulation included eggs retrieved, mature oocytes retrieved, mature oocytes ratio, blastulation rate, and euploid rate. Secondary outcomes for frozen-thawed embryo transfer included pregnancy rate, ongoing pregnancy rate, biochemical pregnancy loss rate, and clinical pregnancy loss rate. RESULTS: Among 222 vaccinated patients and 983 unvaccinated patients who underwent controlled ovarian hyperstimulation cycles between February and September 2021, there was no association on adjusted analysis between COVID-19 vaccination and fertilization rate (ß=0.02±0.02, P=.20) or any of the secondary outcomes assessed: eggs retrieved (ß=0.01±0.57, P=.99), mature oocytes retrieved (ß=0.26±0.47, P=.58), mature oocytes ratio (ß=0.02±0.01, P=.12), blastulation rate (ß=0.02±0.02, P=.27), or euploid rate (ß=0.05±0.03, P=.08). Among 214 vaccinated patients and 733 unvaccinated patients undergoing single euploid frozen-thawed embryo transfer, adjusted analysis demonstrated no significant association between vaccination and clinical pregnancy (adjusted odds ratio [aOR] 0.79, 95% CI 0.54-1.16) or any of the secondary outcomes: pregnancy (aOR 0.88, 95% CI 0.58-1.33), ongoing pregnancy (aOR 0.90, 95% CI 0.61-1.31), biochemical pregnancy loss (aOR 1.21, 95% CI 0.69-2.14), or clinical pregnancy loss (aOR 1.02, 95% CI 0.51-2.06). CONCLUSION: Administration of COVID-19 mRNA vaccines was not associated with an adverse effect on stimulation or early pregnancy outcomes after IVF. Our findings contribute to the growing body of evidence regarding the safety of COVID-19 vaccination in women who are trying to conceive.
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Aborto Espontáneo , Vacunas contra la COVID-19 , COVID-19 , Aborto Espontáneo/epidemiología , Aborto Espontáneo/etiología , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Femenino , Fertilización In Vitro , Humanos , Inducción de la Ovulación , Embarazo , Resultado del Embarazo , Índice de Embarazo , Estudios Retrospectivos , Vacunación , Vacunas Sintéticas , Vacunas de ARNmRESUMEN
Zebrafish have emerged as a major model organism to study vertebrate reproduction due to their high fecundity and external development of eggs and embryos. The mechanisms through which zebrafish determine their sex have come under extensive investigation, as they lack a definite sex-determining chromosome and appear to have a highly complex method of sex determination. Single-gene mutagenesis has been employed to isolate the function of genes that determine zebrafish sex and regulate sex-specific differentiation, and to explore the interactions of genes that promote female or male sexual fate. In this review, we focus on recent advances in understanding of the mechanisms, including genetic and environmental factors, governing zebrafish sex development with comparisons to gene functions in other species to highlight conserved and potentially species-specific mechanisms for specifying and maintaining sexual fate.
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Procesos de Determinación del Sexo/fisiología , Pez Cebra/fisiología , Animales , Femenino , Células Germinativas/metabolismo , Masculino , Procesamiento Proteico-Postraduccional , ARN/metabolismo , Procesos de Determinación del Sexo/genética , Diferenciación Sexual/genética , Pez Cebra/genéticaRESUMEN
Objective: To determine if pregnancy rates (PRs) or pregnancy loss rates (PLRs) were altered in patients undergoing single, euploid frozen-thawed embryo transfer (FET) during the initial peak of the Coronavirus Disease 19 (COVID-19) pandemic. Materials and Methods: This was a retrospective cohort study performed in a single academic center. Patients undergoing single, euploid FET cycles from January to May 2017-2020 were included. Cycles with FET performed in January-May of 2020 ("COVID-surge cohort") were compared to cycles with FET performed in January-May of 2017-2019 ("pre-COVID cohort"). Pregnancy rate (PR), clinical pregnancy rate (CPR), pregnancy loss rate (PLR), and clinical pregnancy loss rate (CLR) were compared between the cohorts. Results: A total of 2629 single, euploid FET cycles were included: 2070 from January to May, 2017-2019 and 559 from January to May 2020. PR was similar when comparing FET performed from January to May 2020 (COVID-surge) to those performed from January to May, 2017-2019 (pre-COVID) (77.6% vs. 73.7%, p = 0.06), while CPR was higher among the COVID-surge compared to the pre-COVID cohort (65.5% vs. 60.0%, p = 0.02). No differences were seen in PLR and CLR among the COVID-surge and pre-COVID cohorts (28.3% vs. 32.0%, p = 0.08; 15.0% vs. 16.5%, p = 0.50). PR, CPR, PLR, and CLR were similar when comparing individual months between the cohorts. Adjusted analysis showed no differences in PR, CPR, PLR, or CLR when comparing the cohorts overall or when comparing corresponding individual months in the two time periods. Conclusion: PRs and PLRs were not decreased when SARS-CoV-2 transmission was widespread in our geographic area, suggesting that high COVID-19 transmission does not compromise early pregnancy outcomes.
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AIM: This study aimed to evaluate the unique phenotype of the Vietnamese polycystic ovarian syndrome (PCOS) population. METHODS: In this multicenter cross-sectional descriptive study, a total of 901 reproductive-age women were recruited at three medical centers in Vietnam from June 2016 to May 2018. Group I included 479 patients with PCOS (Rotterdam 2003 consensus) and Group II included 422 non-PCOS women, consisted of women with regular menstrual cycle, collected at the same time of PCOS recruitment, without ovarian disease or ovarian failure. Main outcome measures were anthropomorphic, serum hormone, ultrasound and physical characteristics of PCOS. RESULTS: The Vietnamese PCOS population was lean, but with a higher weight and body mass index compared to controls. About 34.4% of PCOS subjects had hirsutism, primarily confined to the leg, arm and pubis. The PCOS population had higher serum luteinizing hormone (LH), LH : follicle stimulating hormone ratio, anti-Mullerian hormone and testosterone. The PCOS population had double the ovarian volume compared to controls. PCOS subjects had no increase in metabolic disease history and had on average optimal serum markers for low metabolic disease risk. Group D (O + polycystic ovary morphology [PCOM]) was the most prevalent phenotype noted in our Vietnamese PCOS cohort (67.6%). Modified Ferriman-Gallwey, levels of LH, testosterone and anti-Mullerian hormone were highest in Group A (O + H + PCOM) and lowest in Group D (O + PCOM). CONCLUSION: The Vietnamese PCOS population is characterized by a lean body type, nonfacial hirsutism, anovulatory, enlarged ovaries and typical PCOS serum hormone markers, low risk factors for metabolic syndrome. Nonclassical phenotypes for PCOS were more frequent than the classic phenotype.
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Pueblo Asiatico/estadística & datos numéricos , Síndrome del Ovario Poliquístico/etnología , Adulto , Anovulación/etnología , Anovulación/etiología , Hormona Antimülleriana/sangre , Índice de Masa Corporal , Estudios Transversales , Femenino , Hormona Folículo Estimulante/sangre , Hirsutismo/etnología , Hirsutismo/etiología , Humanos , Hormona Luteinizante/sangre , Ovario/patología , Fenotipo , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/patología , Vietnam , Adulto JovenRESUMEN
STUDY OBJECTIVE: Data are limited regarding optimal timing between operative hysteroscopy and embryo transfer (ET). This study aimed to assess whether the time interval from operative hysteroscopy to ET affects implantation and clinical pregnancy rates. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Private academic center. PATIENTS: All patients who had operative hysteroscopy followed by a day 5 ET from 2012 to 2017. INTERVENTION: Interval of time from operative hysteroscopy to ET. MEASUREMENTS AND MAIN RESULTS: The interval of time from hysteroscopy to ET was calculated, and linear regression analyses were performed to assess the impact on clinical outcome. A subanalysis of patients who underwent subsequent single, euploid, frozen ET(s) was performed. A total of 318 patients were included. Indications for hysteroscopy included polypectomy (nâ¯=â¯205), myomectomy (nâ¯=â¯36), lysis of adhesions (nâ¯=â¯46), septum resection (nâ¯=â¯19), and retained products of conception (nâ¯=â¯12). The mean interval of time from hysteroscopy to ET was 138.4 ± 162.7 days (range, 20-1390). There was no significant difference in mean interval of time between procedure and subsequent ET when comparing patients who achieved and did not achieve implantation. Patients stratified by interval of time from operative hysteroscopy to ET had similar clinical outcomes. The time interval from hysteroscopy had no impact on odds of implantation (odds ratio [OR], 1.001; 95% confidence interval [CI], .999-1.002; pâ¯=â¯.49), ongoing pregnancy (OR, 1.001; 95% CI, .999-1.002; pâ¯=â¯.42), or early pregnancy loss (OR, .997; 95% CI, .994-1.000; pâ¯=â¯.07) (adjusted for oocyte age, recipient age, endometrial thickness, use of preimplantation genetic testing, use of donor egg, fresh vs frozen ET, ET count). Similar results were observed in the subanalysis restricted to euploid single frozen ETs from autologous cycles. CONCLUSION: The time interval from operative hysteroscopy to subsequent ET does not impact the likelihood of successful clinical outcome. Patients who have undergone operative hysteroscopy do not need to delay fertility treatment.
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Implantación del Embrión/fisiología , Transferencia de Embrión , Fertilización In Vitro , Histeroscopía/rehabilitación , Tiempo para Quedar Embarazada , Aborto Espontáneo/epidemiología , Aborto Espontáneo/etiología , Adulto , Estudios de Cohortes , Transferencia de Embrión/métodos , Transferencia de Embrión/estadística & datos numéricos , Femenino , Fertilización In Vitro/métodos , Fertilización In Vitro/estadística & datos numéricos , Humanos , Histeroscopía/efectos adversos , Histeroscopía/estadística & datos numéricos , Embarazo , Resultado del Embarazo/epidemiología , Índice de Embarazo , Estudios Retrospectivos , Factores de Tiempo , Cicatrización de Heridas/fisiologíaRESUMEN
OBJECTIVE: The alpha2C adrenoreceptor deletion 322-325 (ADRA2C del 322-325) polymorphism has been associated with autonomic activity and thermoregulation, which are implicated in the vasomotor symptom (VMS) mechanism. The ADRA2C del (322-325) has higher prevalence in African American women, a group known to experience more frequent and bothersome VMS. We assessed whether the ADRA2C del (322-325) genotype is associated with increased frequency of VMS in African American women. METHODS: DNA samples from African American (Nâ=â400) women participating in the Study of Women's Health Across the Nation (SWAN) were genotyped for the ADRA2C del (322-325) polymorphism. Longitudinal data on VMS were obtained from the SWAN repository. The relation of ADRA2C del (322-325) genotypes (deletion/deletion [D/D]; insertion/deletion [I/D]; insertion/insertion [I/I]) with VMS over the menopausal transition for up to 12 years of follow-up was examined using generalized estimating equations. Primary models considered the outcome of frequent VMS (6 or more days in the prior 2 wk vs VMS <6 d in the prior 2 wk) by stage of menopause. RESULTS: Four hundred DNA samples from African American women were included. Seventy-five women (18.8%) were found to carry the homozygous variant allele (D/D). There was no significant difference in the trajectory of frequent VMS over the menopausal transition between women with D/D and I/I + I/D genotypes (Pâ=â0.39). CONCLUSIONS: In this preliminary study among African American women in SWAN, ADRA2C del (322-325) was not significantly related to self-reported VMS. Further studies are warranted to help us understand the role of the adrenergic system in the physiology of VMS to tailor medical therapy to patient needs.
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Sofocos/genética , Menopausia/fisiología , Receptores Adrenérgicos alfa 2 , Sudoración/genética , Adulto , Negro o Afroamericano , Estudios de Casos y Controles , Estudios Transversales , Femenino , Sofocos/etnología , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Polimorfismo Genético , Encuestas y CuestionariosRESUMEN
BACKGROUND: Cervical cancer is the most prevalent cancer among Peruvian women. Female sex workers (FSW) in Peru are at elevated risk for HPV infection, and receive annual Papanicolaou screening. The objective of this study was to identify barriers to follow-up for abnormal Pap smears among FSW in Peru. METHODS: 97 FSW attending the Alberto Barton Health Center in Lima were surveyed regarding their STI screening history. 17 women with a history of an abnormal Pap smear were interviewed about their experiences regarding follow-up care. RESULTS: Of the 27 HPV-positive women, only 8 (30%) received follow-up treatment. Of the 19 women who did not receive follow-up, 7 (37%) had not been informed of their abnormal result. Qualitative interviews revealed that the major barrier to follow-up was lack of knowledge about HPV and potential health consequences of an abnormal Pap smear. CONCLUSION: HPV infection is highly prevalent in Peruvian FSW, yet only 30% of FSW with abnormal Pap smears receive follow-up care. The predominant barriers to follow-up were lack of standardization in recording and communicating results and insufficient FSW knowledge regarding health consequences of HPV infection. Standardization of record-keeping and distribution of educational pamphlets have been implemented to improve follow-up for HPV.