Advanced Reproductive Age Research Articles

Access to Fertility Care in Geographically Underserved Populations, a Second Look.

Infertility has a prevalence of up to 16% worldwide and is on the rise in developed nations, largely due to pursuing childbearing at advanced reproductive ages. Advances in assisted reproductive technology have benefitted socioeconomically advantaged patients disproportionately. High costs of fertility care are largely responsible for this disparity; however, patients in rural areas also face barriers in accessing both gynecology and reproductive endocrinology subspecialty care. Here, focusing on the USA, we discuss fertility care in geographically underserved areas and low-resource settings, and the impact on reproductive outcomes. Increased innovation to improve patient access to fertility care such as assisted reproductive technology is critical for ensuring equity. Remote monitoring is frequently performed by fertility centers, but partnership with local gynecologists has also been demonstrated to be an effective assisted reproductive technology monitoring method. Telehealth is now in mainstream use and the continued application to reduce geographic barriers to infertility patients is imperative. Partnership between local gynecologists and reproductive endocrinology and infertility specialists may improve patient access to fertility care and provide the unique benefits of continuity and ongoing local social support.

Late motherhood and spatial aspects of late fertility in Slovakia

Abstract Shifting childbearing to later reproductive ages is reflected in all European populations. Late motherhood also changes, from the point of view of parity structure, since nowadays, the beginning of reproductive pathways is increasingly realised at the age of 35 and over more often. The regional dimension of this phenomenon is significantly overlooked, however. The main aim of this paper is to explore how the level and the impact of late motherhood has changed from a spatial perspective. We use Slovakia as a case study population characterised until the end of the 1980s by an early beginning of reproduction and its concentration in the first half of the reproductive period, and by relatively significant socio-economic, cultural and demographic differences. At the same time, we point out the changes in late motherhood in terms of parity structure. Finally, through linear regression models, we try to identify which of the selected factors may condition the differences in share of late fertility and the significance of first births at advanced reproductive ages.

Efficacy of Qizi Yusi Pill on Pregnancy Outcomes in Women of Advanced Reproductive Age: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

To evalvate efficacy of Qizi Yusi Pills (QYP), a Chinese medicine compound preparation, on in vitro fertilization-embryo transfer (IVF-ET) in women of advanced reproductive age. This multicenter, randomized, double-blind, placebo-controlled trial was conducted from June 2018 to October 2019. A total of 124 patients were randomly allocated to either the QYP group or the placebo group using a stratified block randomization design, with 62 patients in each group. All patients completed controlled ovarian stimulation using a standard gonadotropin-releasing hormone agonist (GnRH-a) long protocol. As the QYP group, QYP was administered while the control group received placebo. QYP and placebo were administered for a total of 24 to 30 days from the day of GnRH-a pituitary downregulation to transvaginal oocyte retrieval. Both medications were taken orally at doses of 10 g three times each day. The primary outcome was cumulative pregnancy rate, and the secondary outcomes were periodic medication, follicular status, serum hormone and endometrial receptivity. Follow-up continued until 4 weeks after delivery. Maternal and neonatal complications, such as gestational diabetes, were also observed. Overall, 119 patients completed the study, 60 in the QYP group and 59 in the placebo group. Per protocol (PP) analysis revealed that 6-month cumulative pregnancy rate in the QYP group was significantly higher than that in the placebo group [43.33% (26/60) vs. 25.42% (15/59), P=0.040). Additionally, more oocytes were retrieved from the QYP group than those from the placebo group (8.95 ± 3.12 vs. 7.85 ± 1.91, P=0.022). Moreover, the endometrial thickness of HCG day in the QYP group was significantly higher than that in the placebo group (11.78 ± 2.27 mm vs. 10.68 ± 2.07 mm, P=0.012). Maternal and neonatal complications between the two groups were not significantly different (P>0.05). Intention-to-treat analysis was in line with PP results. QYP can enhance ovarian reserve capacity and ovarian response, and possibly promote endometrial receptivity. QYP effectively improves cumulative pregnancy rates in older patients (⩾35 years) undergoing IVF-ET. (Registration No. ChiCTR1800014427).

The effect of the Ontario Fertility Program on IVF utilization and outcomes in women of advanced reproductive age

Research questionAre the demographics and clinical outcomes similar for patients aged ≥40 but <43 years seeking IVF in Ontario, Canada, before and after implementation of the Ontario Fertility Program (OFP), which supports public funding of IVF up to age 43? DesignRetrospective database review using the Canadian Assisted Reproductive Technologies Registry Plus (CARTR Plus) and Better Outcomes Registry & Network (BORN) Ontario databases. Cycles from women who underwent autologous IVF and who were aged ≥40 and <43 years were analysed during a 2-year period prior to (2014–2015) and after (2016–2017) introduction of publicly funded IVF through the OFP. ResultsThere was an almost doubling of treatment cycles in women aged 40–42 in Ontario after the OFP launch. Clinical pregnancy rate per cycle start (17.0% versus 13.3%, P < 0.001) and cumulative clinical pregnancy rate per stimulation cycle (20.5% versus 16.8%, P < 0.001) were statistically higher in women before OFP implementation. While cumulative live birth rate per cycle start was statistically lower after funding was introduced (12.5% versus 10.5%, P = 0.027), the clinical importance of this difference appears small. Outcomes were above the 10% live birth per cycle threshold recommended by the Advisory Process for Infertility Services panel, commissioned by the Ministry of Health, to determine access to publicly funded IVF. ConclusionsUse of IVF in women over age 40 doubled with access to OFP funding; however, eligibility criteria based on age still meet the target of achieving a cumulative live birth rate of at least 10%.

Extended fertility at highly advanced reproductive age is not related to anti-Müllerian hormone concentrations

Research questionIs extended fertility at the advanced reproductive age of 43–47 years associated with high anti-Müllerian hormone (AMH) concentrations? DesignProspective cohort study including 98 women aged 43–47 years old with a spontaneous conception who were tested for AMH concentrations 1–4 days and 3–11 months post-partum. AMH concentrations at 3–11 months post-partum were further compared with AMH concentrations in healthy age-matched controls that last gave birth at ≤42 years old. Women with current use of combined hormonal contraceptives (CHC), ovarian insult or polycystic ovary syndrome were excluded. Power analysis supported the number of participating women. ResultsMedian AMH concentrations did not differ between the extended fertility (n = 40) and control (n = 58) groups (0.50 versus 0.45 ng/ml, P = 0.51). This remained when analysing by age (≥ or <45 years old). AMH concentrations and women's age did not correlate within the extended fertility group (r = 0.017, P = 0.92); a weak negative correlation was found within the control group (r = –0.23, P = 0.08). AMH was significantly higher 3–11 months post-partum (0.50 ng/ml [0.21–1.23]) than 1–4 days post-partum (0.18 ng/ml [0.06–0.40]), P < 0.001. The two results for each participant were highly correlated (r = 0.82, P < 0.001). The extended fertility and control groups were similar regarding age, age at menarche, past CHC use and history of fertility concern. Parity differed but showed no significant correlation with AMH. ConclusionsSerum AMH concentrations that reflect ovarian reserve do not seem to predict reproductive potential at highly advanced age. Thus, additional factors such as oocyte quality should also be considered in evaluating reproductive potential. AMH suppression that is associated with pregnancy at 1–4 days post-partum recovers at 3–11 months post-partum in women of highly advanced reproductive age.

Outcomes After a Single Ovarian Stimulation Cycle in Women of Advanced Reproductive Age: A Retrospective Analysis.

ObjectivesPrevious studies showed that age is the most important factor that determines the outcome after embryo transfer (ET), with either in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), regardless whether fresh or frozen cycles. The average cumulative live birth rate (CLBR) following a single ovarian stimulation cycle in women of advanced reproductive age (≥38 years of age) has been reported to be 22.6–34.1%. The purpose of this study is to compare the CLBR after a single ovarian stimulation cycle in women of different advanced reproductive age bracket (38/39, 40/41, 42/43 years of age or older), and to explore the factors (e.g., age, type of infertility, body mass index (BMI), ovarian stimulation protocols) associated with CLBR.MethodsThis retrospective analysis included all women of advanced reproductive age (38 years or older) undergoing IVF or ICSI at authors’ institute during a period from January 1, 2016 to December 31, 2018. The study protocol was approved by the Ethics Committee of the Second Hospital of Hebei Medical University (No. 2021-P045). Subjects with underlying diseases were excluded from analysis. The last follow-up was conducted in December 2020, with minimal 2-year follow-up.ResultsThe final analysis included 826 women (40.00 ± 2.10 years of age at the time of ovarian stimulation; n = 633 and 193 for IVF-ET and ICSI-ET, respectively). The number of women in each age bracket was: 424 for 38/39 y, 226 for 40/41 y, 118 for 42/43 y, and 58 for ≥44 y. The number of transferable embryos was 2 (interquartile range: 2,4) for 38/39 y, 2 (2,3) for 40/41 y, 2 (2,3) for 42/43 y, and 2 (1.75,3) for ≥44 y. The rate of fresh embryo transfer was comparable (62.03–72.58%) among the 4 age brackets. The average CLBR following a single cycle was 26.27% in the overall study population, 32.31% for 38/39 y, 26.99% for 40/41 y, 14.4% for 42/43 y, and 3.44% for ≥44 y (P <0.001). In multivariate regression, CLBR was independently associated with younger age (OR for each year: 1.538, 95%CI: 1.193, 1.984) and higher number of transferable embryos (OR for each embryo: 1.495, 95%CI: 1.297, 1.722). CLBR differed significantly in the 38/39 group (P = 0.014), with higher rate in women receiving the Gonadotropin-releasing hormone agonist (GnRH-a) long or GnRH-a ultra-long protocols.ConclusionsForty-two years of age seemed to be a critical cutoff to achieve reasonable level of CLBR after a single ovarian stimulation cycle in women of advanced reproductive age.

Women in Advanced Reproductive Age: Are the Follicular Output Rate, the Follicle-Oocyte Index and the Ovarian Sensitivity Index Predictors of Live Birth in an IVF Cycle?

(1) Background: Several researchers have investigated alternative markers related to ovarian responsiveness in order to better predict IVF outcomes, particularly in advanced reproductive-aged women. The follicular output rate (FORT), the follicle-oocyte index (FOI) and the ovarian sensitivity index (OSI) are among the most promising. However, these three metrics have not been investigated as independent predictors of live birth in women of advanced reproductive age; neither have they been compared to the two ‘component’ characteristics that are used to calculate them. (2) Methods: A logistic regression model containing all relevant predictors of ovarian reserve or response was used to evaluate the potential of FORT, FOI and OSI as predictors of live birth. After, the non-linear associations between FORT, FOI and OSI and the probability of live birth were evaluated. Finally, we fitted multiple logistic regression models to compare whether FORT, FOI and OSI were more informative predictors than their components. (3) Results: 590 couples received a total of 740 IVF cycles, after which, 127 (17.5%) obtained a live birth. None of FORT, FOI and OSI showed a strength of association or a p-value even close to female age (odds ratio for live birth (95% confidence interval) 1.00 (0.99–1.01), 1.00 (0.99–1.01), 0.98 (0.88–1.11) and 0.58 (0.48–0.72), respectively). The three models comparing FORT, FOI and OSI with the number of oocytes retrieved, the AFC, the number of preovulatory follicles and the FSH total dose were not more informative. (4) Conclusions: In a population of women of advanced age with unexplained infertility, none of FORT, FOI and OSI were predictive of live birth or more predictive than the two ‘component’ characteristics that were used to calculate them. We suggest clinicians and researchers still use female age as the most reliable predictor of an IVF treatment.

Gonadotropin-releasing hormone agonist downregulation combined with hormone replacement therapy improves the reproductive outcome in frozen\u2013thawed embryo transfer cycles for patients of advanced reproductive age with idiopathic recurrent implantation failure

BackgroundTo determine whether gonadotropin-releasing hormone (GnRH) agonist downregulation combined with hormone replacement therapy (HRT) can improve the reproductive outcomes in frozen–thawed embryo transfer cycles for older patients (aged 36–43 years) with idiopathic recurrent implantation failure (RIF).MethodsThis retrospective cohort study involved 549 older patients undergoing their third cleavage-stage embryo or blastocyst transfer over a 5-year period (January 2015–December 2020) at Northwest Women’s and Children’s Hospital after in vitro fertilization/intracytoplasmic sperm injection cycles. Patients with known endometriosis or adenomyosis were excluded from the study. The patients were divided into three groups according to the endometrial preparation protocol: the natural cycle (NC) group (n = 65), the HRT group (n = 194), and the GnRH agonist downregulation combined with HRT cycle (GnRH agonist–HRT) group (n = 290). The primary outcome was the live birth rate, and the secondary outcomes were the clinical pregnancy, miscarriage, and ongoing pregnancy rates.ResultsThe live birth rate in the GnRH agonist–HRT group (36.55%) was higher than that in the HRT group (22.16%) and NC group (16.92%) (P < 0.0001). Similarly, a logistic regression model adjusting for potential confounders showed that the live birth rate was higher in the GnRH agonist–HRT group than in the HRT group (odds ratio, 0.594; 95% confidence interval, 0.381–0.926; P = 0.021) and NC group (odds ratio, 0.380; 95% confidence interval, 0.181–0.796; P = 0.010).ConclusionsThe GnRH agonist–HRT protocol improves the live birth rate in frozen–thawed embryo transfer cycles for patients of advanced reproductive age with RIF. We hypothesize that the GnRH agonist–HRT protocol enhances implantation-related factors and promotes optimal endometrial receptivity, leading to an improved live birth rate. These findings are also useful for further investigating the underlying mechanism of the GnRH agonist–HRT protocol in improving the reproductive outcomes for patients of advanced reproductive age with RIF.Trial registrationThis research protocol was approved by the hospital institutional ethics committee (No. 2021002).

In Vivo and In Vitro Matured Oocytes From Mice of Advanced Reproductive Age Exhibit Alternative Splicing Processes for Mitochondrial Oxidative Phosphorylation.

The mean age of women seeking infertility treatment has gradually increased over recent years. This has coincided with the emergence of in vitro maturation (IVM), a method used in assisted reproductive technology for patients with special requirements. However, when compared with conventional in vitro fertilization, IVM is associated with poor embryonic development potential and low live birth rates, thus limiting the widespread application of this technique. In this study, we performed RNA-sequencing transcriptomic assays and identified a total of 2,627 significant differentially expressed genes (DEGs) between IVM oocytes and in vivo matured oocytes from mice of advanced reproductive age. Next, Kyoto Encyclopedia of Genes and Genomes pathway analysis was used to identify the potential functions of the DEGs. The most significantly enriched pathway was oxidative phosphorylation (OXPHOS). In addition, we constructed a protein-protein interaction network to identify key genes and determined that most of the hub genes were mtDNA-encoded subunits of respiratory chain complex I. Antioxidant supplementation lead to an increase in ATP production and reduced the gene expression profile of the OXPHOS pathway in the IVM group. Moreover, alternative splicing (AS) events were identified during in vivo or in vitro oocyte maturation; data showed that skipped exons were the most frequent type of AS event. A number of genes associated with the OXPHOS pathway exhibited alterations in AS events, including Ndufa7, Ndufs7, Cox6a2, Ndufs5, Ndufb1, and Uqcrh. Furthermore, the process of IVO promoted the skipping of exon 2 in Ndufa7 and exon 3 in Ndufs7 compared with the IVM oocytes, as determined by semi−quantitative RT−PCR. Collectively, these findings provide potential new therapeutic targets for improving IVM of aged women who undergo infertility treatment.

Independent Variables for Determining the Cumulative Live Birth Rates of Aged Patients with Polycystic Ovary Syndrome or Tubal Factor Infertility: A Retrospective Cohort Study.

ObjectiveTo assess whether women of advanced age (≥35 years) with polycystic ovary syndrome (PCOS) have the same cumulative live birth rate (CLBR) as their age-matched controls with tubal factor infertility and to determine the influencing factors on the CLBRs of aged women.DesignA retrospective cohort study.Setting and PopulationA total of 160 women of advanced age (≥35 years) with PCOS and 1073 women with tubal factor infertility were included in our study. All patients underwent their first fresh cycles and subsequent frozen cycles within in one year in our centre from 2015 to 2020.MethodsTo determine independent influencing factors on the CLBRs of these aged patients, a multivariable Cox regression model of CLBR according to the transfer cycle type was constructed. Main outcome measure(s): CLBRs.ResultThe Cox regression model of the CLBRs indicated that there was no significant difference between the PCOS group and the tubal infertility group in terms of advanced age (HR, 0.95; 95% CI, 0.71-1.27, P=0.732). The CLBR significantly decreased for women of advanced reproductive age up to 37 years of age (HR, 0.46; 95% CI, 0.39-0.56, P<0.001). The CLBR increased by 63% when more than ten oocytes were retrieved (HR, 1.63; 95% CI, 1.34-1.98, P<0.001). Patients with an AMH level above 32.13pmol/l were likely to have a 72%(HR, 1.72; 95% CI, 1.08-2.73, = 0.023) and 34% (HR, 1.34; 95% CI, 1.07-1.68, P=0.010)improvement in CLBR compared to those with an AMH below 7.85pmol/l and 7.85-32.12pmol/l, respectively.ConclusionDespite the higher number of oocytes retrieved in PCOS patients, the reproductive window is not extended for PCOS patients compared with tubal factor infertility patients. Age, AMH and the number of oocytes retrieved play crucial roles in the CLBRs of patients of advanced age (≥35 years).

OVULATION INDUCTION AND SUCCESSFUL LIVE DELIVERY IN A 46.5-YEAR-OLD WOMAN IN OVERT MENOPAUSE BY RESTORING FOLLICULAR SENSITIVITY TO FOLLICLE STIMULATING HORMONE (FSH)

To try to up-regulate FSH receptors on granulosa-theca cells in a woman of very advanced reproductive age in overt menopause whose FSH receptors had been internalized related to elevated serum FSH levels, by inhibiting release of FSH from the pituitary by negative feedback of estrogen. The overall objective was to deliver a live healthy baby. Ethinyl estradiol (EE) 20 micrograms was given to a woman age 46.5 who had amenorrhea for 9 months and who was in overt menopause, as evidenced by failure to have menses following 10mg medroxyprogesterone acetate x 13 days. In addition, the patient had a serum estradiol (E2) of <15 pg/mL, a serum FSH of 117 mIU/mL, and a serum anti-Mullerian level of <0.09 ng/mL. She was treated with EE to lower serum FSH levels rather than E2 because the former does not contribute to the total serum E2 level, and thus allows the treating physician to detect when a follicle has been recruited by rising serum E2 levels. A rising E2 would dictate the addition of pelvic sonography to help determine when a mature dominant follicle was achieved (18mm average diameter with serum E2 ≥200pg/mL). If a mature follicle was achieved, 1mg granulocyte colony stimulating factor (G-CSF) would be given the day before an injection of 10,000 units human chorionic gonadotropin (hCG) to help the oocyte release. At age 42 she had been treated for infertility and was found to have the luteinized unruptured follicle syndrome. She failed to release the oocyte with either hCG or leuprolide acetate but was successful with hCG when G-CSF was added (and delivered a healthy baby despite a day 3 serum FSH of 47 mIU/mL). Progesterone vaginal suppositories 200mg twice daily was supplemented in the luteal phase. After 44 days of EE she was able to attain a mature follicle (E2 273 pg/mL, follicular size 18.8mm average diameter). She released the oocyte, conceived and successfully delivered a full-term healthy baby. A previous case was reported in Human Reproduction in 2000 of a 45-year-old in overt menopause. Successful reversal of menopause was achieved, and she delivered a live baby utilizing this same technique of restoration of FSH sensitivity by using EE without any exogenous FSH stimulation. Precedents are important for patient-physician decisions regarding treatment options. This case shows a live delivery is possible even in a 46.5-year-old menopausal woman using her own oocytes.

Individual and community factors associated with unintended pregnancies among women of advanced reproductive age in Nigeria

ABSTRACT Studies have examined individual and community level factors associated with unintended pregnancies. However, existing studies tends to focus the general population of reproductive age women without isolating women of advanced reproductive age (women at the age range of 35–49 years) for specific research attention. There is need for specific attention on this group of women because pregnancies among them whether intended or unintended elevate obstetric risks for both mother and child. This study examines associated individual and community factors of unintended pregnancies among women of advanced reproductive age in Nigeria. Data were extracted from the 2018 Nigeria Demographic and Health Survey. A weighted sample of 12,509 women was analyzed. Three multilevel logistic regression models were estimated. The study revealed a 10.3% prevalence of unintended pregnancies. Individual characteristics such as maternal age, number of living children, delayed marriage, and community characteristics such as high community poverty and high community unmet contraceptive need were significantly associated with unintended pregnancies. Variations in unintended pregnancies across the communities were more attributable to individual factors. Interventions should develop specific strategies tailored toward women of advanced reproductive age.

Вакцина Гам-КОВИД-Вак (Спутник V) не оказывает негативного влияния на овариальный резерв у женщин репродуктивного возраста

Relevance. There is limited evidence on the effect of various vaccines on the human reproductive system. Potential adverse effects of vaccines on fertility are associated with autoimmune disorders, which might cause gonadal damage. Currently, several studies are underway investigating the impact of COVID-19 vaccines on human fertility. To our best knowledge, there is only one study published which demonstrated no adverse effects of the COVID-19 vaccine on assisted reproductive technology outcomes. Aim. To investigate the effect of the Gam-COVID-Vac (Sputnik V) vaccine on ovarian reserve and antiphospholipid antibody level in reproductive-age women. Materials and methods. The prospective study included 51 women vaccinated against COVID-19 with Gam-COVID-Vac (Sputnik V) vaccine. The inclusion criteria were age from 18 to 45, preserved menstrual function, normal ovarian reserve, no history of COVID-19, negative PCR test result for SARS-CoV-2 and negative SARS-CoV-2 IgG antibody test before vaccination, no pregnancy, and no history of serious illnesses. Clinical evaluation was carried out twice-immediately before immunization and 90 days after the first vaccine component administration. The antral follicle count was measured by pelvic ultrasound. Serum levels of AMH, FSH, TSH, estradiol, antiphospholipid antibodies (aPL) M and G isotypes against cardiolipin (aCL), β2-glycoprotein-1 (aβ2-GP-1), annexin V (aAn V), phosphatidylserine (aPS), and IgG antibodies against SARS-CoV-2 were measured by enzyme immunoassay. Results. There were no significant changes in hormones levels and antral follicle counts before and after vaccination, including in women of advanced reproductive age (≥37 years). After immunization, aPL antibody levels did not differ significantly from the baseline. There was no correlation between aPL antibody level dynamics and level of FSH and AMH, which indirectly demonstrates no possible autoimmune effect of vaccination on women's fertility. Conclusion. This is the first study investigating the effect of the Gam-COVID-Vac vaccine on ovarian reserve parameters and aPL antibody levels. The preliminary results prove that the Gam-COVID-Vac vaccine in women of reproductive age does not adversely impact ovarian reserve.

GROWING PAINS: CAN HUMAN GROWTH HORMONE REALLY IMPROVE BLASTOCYST QUALITY SCORE?

GROWING PAINS: CAN HUMAN GROWTH HORMONE REALLY IMPROVE BLASTOCYST QUALITY SCORE?

Case Report: Acupuncture in Infertile Women of Advanced Reproductive Age with Low AMH

Female reproductive aging is a common cause of infertility in women in their late 30s and 40s [1] Because female fertility begins to decline in women of advanced reproductive age (≥ 35 years old), advanced reproductive age (ARA) is a risk factor for female infertility, pregnancy loss, fetal anomalies, stillbirth, and obstetric complications [2]. This article reviews on 10 clinical cases of Canadian women who are infertile due to advanced reproductive age with low AMH level (<1 ng/ml), and, who, after several failed IUI or IVF cycles, were treated with acupuncture for 3 to 6 months. All 10 women had spontaneous pregnancies and live births. Acupuncture is effective for patients of advanced reproductive aged with low AMH who did not respond to IUI or IVF protocol. Method: based on weekly treatments, the 12 course-treatment of acupuncture focussed on invigorating kidney qi and nourishing the spleen and stomach in order to increase the probability of the outcomes of pregnancy and live birth by regulating menstruation and ovulation, and improving egg quality.

Never too late? Quadruplets at the age of 65\xa0years

BackgroundWe discuss the challenges of multiple pregnancy at very advanced reproductive age.Case presentationWe present the case of a quadruplet pregnancy at the maternal age of 65 following in-vitro fertilization (IVF) with donor eggs and sperm, involving cross-border reproductive care. All children born were at 25 weeks’ gestation and survived; however, poor neurodevelopmental outcome remains a major concern in one child.ConclusionsThe use of reproductive technology to achieve a multiple pregnancy at such an advanced post-menopausal age generated a debate on ethical, psychosocial and medical questions. We share this debate and highlight the need to reconsider international guidelines for women of advanced reproductive age.

Immature Follicular Origins and Disrupted Oocyte Growth Pathways Contribute to Decreased Gamete Quality During Reproductive Juvenescence in Mice.

Egg quality dictates fertility outcomes, and although there is a well-documented decline with advanced reproductive age, how it changes during puberty is less understood. Such knowledge is critical, since advances in Assisted Reproductive Technologies are enabling pre- and peri-pubertal patients to preserve fertility in the medical setting. Therefore, we investigated egg quality parameters in a mouse model of the pubertal transition or juvenescence (postnatal day; PND 11–40). Animal weight, vaginal opening, serum inhibin B levels, oocyte yield, oocyte diameter, and zona pellucida thickness increased with age. After PND 15, there was an age-associated ability of oocytes to resume meiosis and reach metaphase of meiosis II (MII) following in vitro maturation (IVM). However, eggs from the younger cohort (PND 16–20) had significantly more chromosome configuration abnormalities relative to the older cohorts and many were at telophase I instead of MII, indicative of a cell cycle delay. Oocytes from the youngest mouse cohorts originated from the smallest antral follicles with the fewest cumulus layers per oocyte, suggesting a more developmentally immature state. RNA Seq analysis of oocytes from mice at distinct ages revealed that the genes involved in cellular growth signaling pathways (PI3K, mTOR, and Hippo) were consistently repressed with meiotic competence, whereas genes involved in cellular communication were upregulated in oocytes with age. Taken together, these data demonstrate that gametes harvested during the pubertal transition have low meiotic maturation potential and derive from immature follicular origins.

Sonographic and clinical features of adenomyosis in women in "early" (18-35) and "advanced" (&gt;35) reproductive ages

Adenomyosis has been considered for a long time a condition of advanced reproductive age. Recently, imaging techniques have allowed its diagnosis in young women. The aim of our study was to compare adenomyosis in early (18-35) and advanced (>35) reproductive age (ERA vs. ARA). Between May 2019 and October 2020, 928 consecutive women underwent transvaginal ultrasounds (TV-US) in our Department. We enrolled 134 women of reproductive age (18-55) presenting at least 2 US features of adenomyosis, according to the MUSA consensus. We compared the two reproductive age groups (ERA and ARA) about both clinical and US features of adenomyosis. Severe dysmenorrhea was more frequent in the ERA group (78.7% vs. 54.8%), while menorrhagia was more frequent in the ARA group (64.4% vs. 37.7%). At US, the ARA group had a higher frequency of altered junctional zone (67.1% vs. 39.3%), diffuse (76.7% vs. 39.3%) and severe adenomyosis (24.7% vs. 9.8%), and adenomyoma (16.4% vs. 1.6%). Adenomyosis may occur in young women, who present different clinical and sonographic features compared to older women. Young patients have a higher prevalence of severe dysmenorrhea and focal and mild adenomyosis at US, while older women present more frequently menorrhagia, and altered junctional zone, diffuse and severe adenomyosis at US. Early diagnosis in young women suffering from adenomyosis may help to interrupt the mechanisms that drive the development of adenomyosis, starting immediately the right treatment.

Influência da paridade no desenvolvimento da depressão em mulheres brasileiras

Objetivo: Analisar a relação entre paridade e depressão em mulheres em idade reprodutiva entrevistadas na Pesquisa Nacional de Saúde, 2013. Metodologia: Estudo transversal, de base populacional realizado com base nos dados da Pesquisa Nacional de Saúde Brasileira (PNS) – 2013. Foram incluídos registros de mulheres em período reprodutivo, com idade entre 18 e 49 anos, totalizando a amostra com 15.344 mulheres. Resultados: Observou-se associação bruta estatisticamente significante entre a paridade e depressão (RP= 1.32; IC 95%: 1.20 - 1.46). Houve também associação entre ter filhos com baixo peso e depressão (RP= 1.64; IC 95%: 1.24 - 2.18). Mostrando que mulheres em idade reprodutiva mais velhas e com 3 filhos ou mais apresentam 36 vezes mais chances de referir diagnóstico médico de depressão, e aquelas que tiveram filho com baixo peso essa probalidade quase se duplicou. Conclusão: Mulheres em idade reprodutiva mais avançada, que tiveram maior paridade, tiveram mais chances de apresentarem depressão, havendo uma potencialização dessa condição quando tiveram filhos de baixo peso. Assim, ressalta-se a importância de conhecer e compreender os determinantes e condicionantes da saúde que estão associados ao processo de vulnerabilização e adoecimento feminino, para implementar estratégias de intervenção pertinentes no manejo da depressão, em todos os níveis de atenção à saúde.

Exploratory analysis of serum concentrations of oocyte biomarkers growth differentiation factor 9 and bone morphogenetic protein 15 in ovulatory women across the menstrual cycle

To characterize and evaluate the variation in serum concentrations of oocyte-secreted growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) throughout the menstrual cycle in women from young to advanced reproductive ages. Cross-sectional, observational, and exploratory study. Multicenter university-based clinical practices and laboratories. Serum was collected every 1-3 days throughout the menstrual cycle from 3 cohorts of healthy, ovulatory women: menses to late luteal phase (21-29 years of age; n = 16; University of Otago) and across one interovulatory interval (18-35 years of age; n = 10; and 45-50 years of age; n = 15; University of Saskatchewan). None. To detect the changes in serum GDF9 and BMP15 across the cycle, mean concentration and variance were statistically modeled using a generalized additive model of location, shape and scale (GAMLSS). Follicle-stimulating hormone, luteinizing hormone, estradiol, progesterone, and anti-Müllerian hormone were also assessed. GDF9 and BMP15 were detectable in 54% and 73% of women and varied 236-fold and 52-fold between women, respectively. Across the menstrual cycle, there were minimal changes in GDF9 or BMP15 within a woman for all cohorts, with no significant differences detected in the modeled mean concentrations. However, modeled variances were highest in the luteal phases of all women for BMP15 immediately after ovulation, regardless of age. Serial changes in GDF9 or BMP15 concentrations across the cycle were not statistically detected and are likewise similar across the reproductive lifespan. Further research is required to fully elucidate the utility of these oocyte biomarkers at diagnosing fertility potential and/or disease.