Infertility: a marker of future health risk in women? Infertility, may be a harbinger for future health risk in women, including early mortality. Fertility status itself could serve as an early biomarker, (present in a woman's reproductive years) for risk stratification later in life. The relationship between infertility and early mortality involves the impact of nulliparity on future adverse health events, potential sequelae from the underlying cause(s) of infertility, the risks of fertility treatments, as well as the potential for risk reduction from a healthy pregnancy.
Role of the uterus in fertility, pregnancy, and developmental programming The extent to which the uterine endometrium contributes to the success of fertility treatments has long been debated. Several uterine conditions have been associated with poor endometrial receptivity and low pregnancy rates (1). Thin endometrium, fibroids, adenomyosis, and endometriosis, for example, can each affect uterine receptivity and limit the ability to conceive. Many of these conditions are commonly seen in the infertile population and many may go undiagnosed. In the absence of obvious defects, the contribution of uterine receptivity to in vitro fertilization success has been controversial; the uterus and eggs are linked in most women undergoing in vitro fertilization making it difficult to discern the relative contribution of the egg verses the endometrium.
Introduction Infertility has long-term effects beyond the inability to conceive. Infertility may be a harbinger of future disease and altered longevity. Understanding the mechanisms of how fertility is a window to health opens new avenues of important investigation addressing interdependent physiologic processes. Identification of healthy persons at risk for future cardiovascular disease, diabetes, or cancer could allow a change in reproductive medical care by altering long-term surveillance and reduction of risk.
Pros and cons of robotic microsurgery as an appropriate approach to male reproductive surgery for vasectomy reversal and varicocele repair Vasectomy reversal is a technically demanding procedure. Since the introduction of the operating microscope in 1975 for this kind of surgery, there has been an improvement in success rates (1, 2). The use of the operative microscope to achieve greater fertility rates and vas patency after vasovasostomy has become a standard for the microsurgeon who treats male infertility (2). However, this technique requires a great degree of microsurgical training and a skilled surgical assistant. The development of robotic assisted procedures in several surgical fields continues to expand (3–7).
Preimplantation genetic testing for aneuploidy: costly or cost effective? We have read with great interest the study by Neal et al. (1) where the authors compared the cumulative in vitro fertilization (IVF)-related costs to achieve a live birth or exhaust an embryo cohort obtained from a single-oocyte retrieval in women with and without preimplantation genetic testing for aneuploidy (PGT-A) testing. This rigorous model demonstrates that PGT-A testing results in an overall cost savings per live birth, shorter duration of treatment, fewer failed embryo transfers, fewer clinical miscarriages and similar cumulative live birth rates.
Beyond fertility: polycystic ovary syndrome and long-term health Polycystic ovary syndrome (PCOS) is a reproductive, endocrine, and metabolic disorder affecting millions of women worldwide. Women with PCOS are often identified in adolescence or early adulthood with symptoms of oligomenorrhea or hirsutism or when presenting for infertility care. The health risks associated out of PCOS, however, go far beyond management of these common presenting symptoms or fertility treatment and likely extend past the reproductive years through and beyond menopause. International surveys suggest that most patients are dissatisfied with long-term counseling related to medical and psychologic issues.
Fertility treatment and congenital urologic malformations: is there a solution to our correlation versus causation woes? In their recent study, Arendt et al. (1), used data from 80,220 live born singleton boys from the Danish National Birth Cohort and the Aarhus Birth Cohort to investigate the relationship between parental subfertility and risk of cryptorchidism and hypospadias in offspring. Combining data across multiple cohorts gives their study adequate power to detect differences in risk between offspring conceived with the help of fertility treatments and those naturally conceived. Fertility treatment was self-reported and included intrauterine insemination (IUI) and in vitro fertilization (IVF).
Male infertility as a window to health There is an emerging body of evidence suggesting that male infertility may be a harbinger of future health. Potential associations between infertility and health may arise from genetic, developmental, and lifestyle factors. Studies have explored possible links between male infertility and oncologic, cardiovascular, metabolic, and autoimmune diseases. Male infertility may also be a predictor of hospitalization and mortality. Additional research is required to elucidate the mechanisms by which male infertility affects overall health.
An improvement in surgical technique or a sham? Value of robotic assistance for male reproductive surgery Microsurgical approaches for male reproductive surgery have become the gold standard approach for vasectomy reversal and varicocele repair by fellowship-trained male reproductive surgeons. There is little doubt that outcomes are superior with microsurgical compared to non-microsurgical approaches (1). Indeed, because of the small size of epididymal tubules, it is not possible to perform end to side vasoepididymostomies without optical magnification. Similarly, there have been significant improvements in outcomes with the application of optical magnification to varicocele repair.
Cardiovascular health and ovarian aging One in three American women will die from cardiovascular disease (CVD), making it the leading cause of death among women in the United States. Traditionally, CVD has been seen as a disease of postmenopausal women, yet increasingly, risk factors for CVD are being characterized earlier. Although menopause, and its associated hypoestrogenism, has been consistently linked to CVD risk, accelerated ovarian aging among premenopausal patients has become a focus of attempts to identify women with increased CVD risk earlier.
Ovarian reserve, endometriomas, and surgery: research must go on In this issue of Fertility and Sterility, Muzii et al. (1) present results of a meta-analysis on the peripheral levels of antimüllerian hormone (AMH) in women carrying ovarian endometriomas. They show that these levels are lower compared to controls thus indirectly suggesting that the reported damage to the ovarian reserve observed after surgery for endometriomas may, at least in part, precedes the intervention (2). These results are of great interest and solve a long-standing controversy, but they must be interpreted cautiously and within a more comprehensive vision of the argument.
Pores for thought: preimplantation genetic testing using a nanopore-based DNA sequencer The genetic factor having the most potent influence on embryonic potential is chromosomal status (aneuploid or euploid). Numerous studies have conclusively shown that aneuploidy can be observed in most in vitro fertilization (IVF) embryos that fail to implant and that it is the underlying cause of most miscarriages. It therefore seems reasonable to speculate that screening embryos for such abnormalities should enable the identification of those having the greatest implantation potential. This idea forms the basis of preimplantation genetic testing for aneuploidy (PGT-A).
Position statement on West Nile virus: a committee opinion Although there is currently no definitive evidence linking West Nile virus (WNV) transmission with reproductive cells, it is recommended that practitioners defer gamete donors who have confirmed or suspected WNV infections. This document replaces the previously published document of the same name, last published in 2016 (Fertil Steril 2016;105:e9-10).
A new era in diagnosing adenomyosis is coming Adenomyosis is a frequent gynecological disease, characterized by the migration of glands and stroma from basal layer of the endometrium to the myometrium. Until now the concept that this disease could be diagnosed only by histology was very diffused. Since this disease is often found in women over 40 years of age who underwent hysterectomy, it was common thinking that it was not a real disease. Imaging (magnetic resonance imaging and ultrasound) showed that adenomyosis had a typical appearance (1) and that this could also be detected in younger women with or without typical symptoms.
Quest for a less invasive approach to preimplantation genetic testing remains ongoing Recent years have seen a dramatic uptake in the utilization of preimplantation genetic testing (PGT), both for aneuploidy screening (PGT-A) and for detection of monogenic diseases (PGT-M). Although methodologies have evolved over time, one aspect has remained the same: the need for an embryo biopsy to obtain DNA. Given that embryo biopsy is invasive, costly, and requires technical skill, there is an ongoing quest for alternative sources of embryo-derived DNA. Two sources which have gained substantial attention are blastocoel fluid and spent embryo culture media.
Opioid prescribing after oocyte-retrieval: a time for caution In this issue of Fertility and Sterility, Bortoletto et al. (1) present data on opioid dispensing after oocyte retrieval that should be eye opening to anyone who has been paying attention to the current opioid epidemic. Overprescribing of opioids leads to increased risk to not only the person to whom the opioids are prescribed but also to the community at large. As the authors point out in the introduction, most people developing a heroin use disorder (80%) began with misuse of prescription opioids.
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