Biological versus chronological ovarian age:implications for assisted reproductive technology

<p>Abstract</p> <p>Background</p> <p>Women have been able to delay childbearing since effective contraception became available in the 1960s. However, fertility decreases with increasing maternal age. A slow but steady decrease in fertility is observed in women aged between 30 and 35 years, which is followed by an accelerated decline among women aged over 35 years. A combination of delayed childbearing and reduced fecundity with increasing age has resulted in an increased number and proportion of women of greater than or equal to 35 years of age seeking assisted reproductive technology (ART) treatment.</p> <p>Methods</p> <p>Literature searches supplemented with the authors' knowledge.</p> <p>Results</p> <p>Despite major advances in medical technology, there is currently no ART treatment strategy that can fully compensate for the natural decline in fertility with increasing female age. Although chronological age is the most important predictor of ovarian response to follicle-stimulating hormone, the rate of reproductive ageing and ovarian sensitivity to gonadotrophins varies considerably among individuals. Both environmental and genetic factors contribute to depletion of the ovarian oocyte pool and reduction in oocyte quality. Thus, biological and chronological ovarian age are not always equivalent. Furthermore, biological age is more important than chronological age in predicting the outcome of ART. As older patients present increasingly for ART treatment, it will become more important to critically assess prognosis, counsel appropriately and optimize treatment strategies. Several genetic markers and biomarkers (such as anti-Müllerian hormone and the antral follicle count) are emerging that can identify women with accelerated biological ovarian ageing. Potential strategies for improving ovarian response include the use of luteinizing hormone (LH) and growth hormone (GH). When endogenous LH levels are heavily suppressed by gonadotrophin-releasing hormone analogues, LH supplementation may help to optimize treatment outcomes for women with biologically older ovaries. Exogenous GH may improve oocyte development and counteract the age-related decline of oocyte quality. The effects of GH may be mediated by insulin-like growth factor-I, which works synergistically with follicle-stimulating hormone on granulosa and theca cells.</p> <p>Conclusion</p> <p>Patients with biologically older ovaries may benefit from a tailored approach based on individual patient characteristics. Among the most promising adjuvant therapies for improving ART outcomes in women of advanced reproductive age are the administration of exogenous LH or GH.</p

Couples with non-obstructive azoospermia are interested in future treatments with artificial gametes

STUDY QUESTION: Would couples diagnosed with non-obstructive azoospermia (NOA) consider two future treatments with artificial gametes (AGs) as alternatives for testicular sperm extraction followed by ICSI (TESE-ICSI)? SUMMARY ANSWER: Most couples with NOA (89%) would opt for treatment with AGs before attempting TESE-ICSI and/or after failed TESE-ICSI. WHAT IS KNOWN ALREADY: Couples with NOA who undergo TESE-ICSI have a 25% chance of conceiving a child. Two future treatments that are being developed are 'ICSI with artificial sperm formed from somatic cells' (ICSI with AGs) and 'natural conception after autotransplantation of in vitro proliferated spermatogonial stem cells' (natural conception with AGs). It is unknown what treatment preferences patients have. STUDY DESIGN, SIZE, DURATION: A cross-sectional survey conducted in 2012-2013, addressing all 921 couples diagnosed with NOA and treated with TESE-ICSI in Dutch fertility clinics between 2007 and 2012. The coded questionnaires were sent by mail and followed up with two reminders. PARTICIPANTS/MATERIALS, SETTING, METHODS: We developed the questionnaire based on a literature review and previous qualitative interviews, and included treatment preference and the valuation of nine treatment characteristics. We assessed reliability of the questionnaires and calculated mean importance scores (MISs: 0-10) of each treatment characteristic. We assessed which patient and treatment characteristics were associated with a couple's hypothetical treatment preference using binominal regression. MAIN RESULTS AND THE ROLE OF CHANCE: The vast majority (89%) of the 494 responding couples (response rate: 54%) would potentially opt for AGs as a first and/or a last resort treatment option. More specifically, as a first treatment couples were likely (67%) to prefer natural conception with AGs over TESE-ICSI and less likely to prefer ICSI with AGs over TESE-ICSI (34%). After failed TESE-ICSI, the majority of couples (75%) would want to attempt ICSI with AGs as a last resort option. The most important characteristics of treatment were safety for children (MIS: 8.2), pregnancy rates (MIS: 7.7) and curing infertility (MIS: 6.8). Costs, burden, naturalness and technological sophistication were of about equal importance (MIS: 3.1-4.0). The majority of patients rated conception at home and moral acceptability as not important (MIS: 1.7 and 0.8, respectively), but the importance attributed to these variables did still affect patients' likeliness to opt for AGs. LIMITATIONS AND REASONS FOR CAUTION: Couples with NOA not opting for TESE-ICSI were not included and might have other perspectives. Couples' hypothetical choices for AGs might differ from their actual choices once data on the costs, safety and pregnancy rates become available from these new treatment options. WIDER IMPLICATIONS OF THE FINDINGS: The interest of couples with NOA in potential future treatments with AGs encourages further pre-clinical research. Priority setting for research and future decision-making on clinical application of AGs should take all characteristics important to patients into account. STUDY FUNDING/COMPETING INTERESTS: The authors report no financial or other conflict of interest relevant to the subject of this article.status: publishe