Poor ovarian reserve and male infertility in a rural in vitro fertilization setup: a case report

Female fertility begins to decline many years prior to the onset of menopause despite continued regular ovulatory cycles. Although there is no strict definition of advanced reproductive age in women, infertility becomes more pronounced after the age of 35. In the female, the number of oocytes decreases with age until the menopause. Oocyte quality also diminishes, due in part to increased aneuploidy because of factors such as changes in spindle integrity. Although older male age affects the likelihood of conception, abnormalities in sperm chromosomes and in some components of the semen analysis are less important than the frequency of intercourse. Age is as accurate as any other predictor of conception with assisted reproductive technology.

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?

BackgroundSeveral researches 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 been compared to the two ‘component’ characteristics that were used to calculate them.MethodsA 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 was evaluated. Finally, we fitted multiple logistic regression models to compare whether FORT, FOI and OSI were more informative predictors than the two ‘components’ used to calculate them. Results590 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 two ‘components’ used to calculate them were not more informative.Conclusion(s)In a population of women of advanced age with unexplained infertility, none of FORT, FOI and OSI were predictive of live birth and more predictive than the two ‘components’ characteristics that were used to calculate them. We suggest clinicians and researchers still to use female age as the most reliable predictor of an IVF treatment.Trial registrationretrospectively registered

Recombinant human luteinizing hormone co-treatment in ovarian stimulation for assisted reproductive technology in women of advanced reproductive age: a systematic review and meta-analysis of randomized controlled trials

Introduction Several studies suggest that luteinizing hormone (LH) could improve IVF outcome in women of advanced reproductive age by optimizing androgen production. In this review, we assessed the role of recombinant-human LH (r-hLH) and recombinant human follicle stimulating hormone (r-hFSH) co-treatment in ovarian stimulation for assisted reproductive technology in women of advanced reproductive age candidates for assisted reproduction. Material and methods Using a preregistered protocol we systematically searched Medline/PubMed, Scopus and the ISI Web of Science databases to identify randomized controlled trials in which r-hFSH monotherapy protocols were compared with r-hFSH/r-hLH co-treatment in women ≥35 years undergoing fresh IVF cycles. We calculated the pooled odds ratio (OR) for dichotomous data and the weight mean difference (WMD) for continuous data with an associated 95% confidence interval (CI). The meta-analyses were conducted using the random-effect model. P values < 0.05 were considered statistically significant. Subgroup analyses of all primary and secondary outcomes were performed only in women aged 35–40 years. Results Twelve studies were identified. In women aged between 35 and 40 years, r-hFSH/r-hLH co-treatment was associated with higher clinical pregnancy rates (OR 1.45, CI 95% 1.05–2.00, I2 = 0%, P = 0.03) and implantation rates (OR 1.49, CI 95% 1.10–2.01, I2 = 13%, P = 0.01) versus r-hFSH monotherapy. Fewer oocytes were retrieved in r-hFSH/r-hLH-treated patients than in r-hFSH-treated patients both in women aged ≥35 years (WMD -0.82 CI 95% -1.40 to − 0.24, I2 = 88%, P = 0.005) and in those aged between 35 and 40 years (WMD -1.03, CI − 1.89 to − 0.17, I2 = 0%, P = 0.02). The number of metaphase II oocytes, miscarriage rates and live birth rates did not differ between the two groups of women overall or in subgroup analysis. Conclusion Although more oocytes were retrieved in patients who underwent r-hFSH monotherapy, this meta-analysis suggests that r-hFSH/r-hLH co-treatment improves clinical pregnancy and implantation rates in women between 35 and 40 years of age undergoing ovarian stimulation for assisted reproduction technology. However, more RCTs using narrower age ranges in advanced age women are warranted to corroborate these findings.

Never too late? Quadruplets at the age of 65 years

Background We discuss the challenges of multiple pregnancy at very advanced reproductive age. Case presentation We 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. Conclusions The 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.

Never too late? - Quadruplets at the age of 65 years

Background We discuss the challenges of multiple pregnancy at very advanced reproductive age. Case Presentation We 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. Conclusions The 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.

Correlates and Timing of Reproductive Aging Transitions in a Global Cohort of Midlife Women With Human Immunodeficiency Virus: Insights From the REPRIEVE Trial

Background Reproductive aging may contribute to cardiometabolic comorbid conditions. We integrated data on gynecologic history with levels of an ovarian reserve marker (anti-müllerian hormone [AMH)] to interrogate reproductive aging patterns and associated factors among a subset of cisgender women with human immunodeficiency virus (WWH) enrolled in the REPRIEVE trial. Methods A total of 1449 WWH were classified as premenopausal (n = 482) (menses within 12 months; AMH level ≥20 pg/mL; group 1), premenopausal with reduced ovarian reserve (n = 224) (menses within 12 months; AMH &lt;20 pg/mL; group 2), or postmenopausal (n = 743) (no menses within12 months; AMH &lt;20 pg/mL; group 3). Proportional odds models, adjusted for chronologic age, were used to investigate associations of cardiometabolic and demographic parameters with reproductive aging milestones (AMH &lt;20 pg/mL or &gt;12 months of amenorrhea). Excluding WWH with surgical menopause, age at final menstrual period was summarized for postmenopausal WWH (group 3) and estimated among all WWH (groups 1–3) using an accelerated failure-time model. Results Cardiometabolic and demographic parameters associated with advanced reproductive age (controlling for chronologic age) included waist circumference (&gt;88 vs ≤88 cm) (odds ratio [OR], 1.38; 95% confidence interval, 1.06–1.80; P = .02), hemoglobin (≥12 vs &lt;12 g/dL) (2.32; 1.71–3.14; P &lt; .01), and region of residence (sub-Saharan Africa [1.50; 1.07–2.11; P = .02] and Latin America and the Caribbean [1.59; 1.08–2.33; P = .02], as compared with World Health Organization Global Burden of Disease high-income regions). The median age (Q1, Q3) at the final menstrual period was 48 (45, 51) years when described among postmenopausal WWH, and either 49 (46, 52) or 50 (47, 53) years when estimated among all WWH, depending on censoring strategy. Conclusions Among WWH in the REPRIEVE trial, more advanced reproductive age is associated with metabolic dysregulation and region of residence. Additional research on age at menopause among WWH is needed. Clinical Trials Registration NCT0234429.

Women of Advanced Reproductive Age and Maternal Health Outcomes: A Review of the Literature

Women of advanced reproductive age (ARA) constitute a growing proportion globally, as more women delay entry into motherhood, in a bid to accommodate their educational and career goals. Social, economic and technological realities propel women to postpone childbearing to a later and more convenient age. What are the maternal outcomes of such delays? This paper reviewed studies that have examined the association between advanced reproductive age and maternal health outcomes. It also attempts to develop a conceptual framework regarding relationship between ARA and maternal outcomes. The Google Scholar search engine was used to search for published studies on the subject in the last ten years. A total of 40 studies were sampled, of which the majority were retrospective studies, using secondary data, in particular health institutes reports. Only 17% of the studies was conducted in Nigeria, and none by social scientists. Ninety percent (90%) of the studies reviewed, established that advanced reproductive age predisposes women to adverse reproductive events. Some of the maternal, and per-natal outcomes include; spontaneous abortion, pre-eclampsia, eclampsia, gestational diabetes, antepartum hemorrhage, postpartum hemorrhage, intrauterine growth restriction, obstructed labour, caesarean delivery, placenta abruption and, congenital abnormalities. Others are, – low birth weight, fetal distress, mal-presentation, perinatal lacerations, preterm births, stillbirth, early neonatal death, perinatal and maternal mortality. The study recommends the needs for sociological studies to compliment the discourse on ARA and the maternal health outcomes from the social angle.