Paternal age and reproduction

BACKGROUND Due to various sociological factors, couples in developed countries are increasingly delaying childbearing. Besides ethical, economical and sociological issues, this trend presents us with several complex problems in reproduction. Although it is well-known that maternal age has a negative effect on fertility and increases the risk of adverse outcome during pregnancy and in offspring, the paternal influence on these outcomes is less well researched and not well-known. METHODS We performed a systematic search of PubMed, and retrieved original articles and review articles to update our previous survey in this journal. RESULTS This review highlights the link between male age and genetic abnormalities in the germ line and summarizes the knowledge about the effects of paternal age on reproductive function and outcome. Increasing paternal age can be associated with decreasing androgen levels, decreased sexual activity, alterations of testicular morphology and a deterioration of semen quality (volume, motility, morphology). Increased paternal age has an influence on DNA integrity of sperm, increases telomere length in spermatozoa and is suggested to have epigenetic effects. These changes may, at least in part, be responsible for the association of paternal age over 40 years with reduced fertility, an increase in pregnancy-associated complications and adverse outcome in the offspring. CONCLUSION Although higher maternal age can be an indication for intensive prenatal diagnosis, including invasive diagnostics, consideration of the available evidence suggests that paternal age itself, however, provides no rationale for invasive procedure

Effects of interleukin-1 receptor antagonism in women with polycystic ovary syndrome—the FertIL trial

Introduction: Chronic low-grade inflammation might contribute to hyperandrogenemia and metabolic complications in polycystic ovary syndrome (PCOS). The proinflammatory cytokine interleukin (IL)-1 stimulates androgen production from ovarian cells, whereas blockade of the IL-1 pathway improves cardiometabolic health. We aimed to investigate whether blocking the IL-1 pathway ameliorates hyperandrogenemia in patients with PCOS. Methods: This is a prospective, interventional, single-arm, proof-of-concept trial performed at a tertiary hospital in Switzerland (August 2018 to July 2020) in 18 premenopausal women with a diagnosis of PCOS according to the Rotterdam criteria, total testosterone levels ≥ 1.7 nmol/L, and C-reactive protein (CRP) ≥ 1.0 mg/L. Patients received 100 mg/day of the IL-1-receptor antagonist anakinra for 28 days and underwent weekly blood sampling until 1 week after the end of treatment. The primary endpoint was the change in serum androstenedione levels on day 7 of treatment, assessed with liquid chromatography–tandem mass spectrometry. Seven of these women participated in a subsequent observational sub-study (May 2021 to December 2021). Results: Median [interquartile range (IQR)] androstenedione increased by 0.5 [−0.1, 1.6] nmol/L (p = 0.048) with anakinra and by 1.3 [0.08, 2.4] nmol/L [p = 0.38] without anakinra between baseline and day 7. Anakinra reduced CRP levels on days 7, 21, and 28 (p < 0.001) but did not lead to an absolute reduction in androgens. However, four of six patients (67%) had smaller areas under the curves for androstenedione and/or testosterone during the 28-day intervention with anakinra as compared to 28 days without treatment. Discussion: Our findings suggest that anakinra suppresses IL-1-mediated chronic low-grade inflammation in PCOS and might attenuate biochemical hyperandrogenemia

Chronic low-grade inflammation in polycystic ovary syndrome: is there a (patho)-physiological role for interleukin-1?

The polycystic ovary syndrome (PCOS) is a frequent endocrine disorder in women of reproductive age. Its main characteristics are the ovarian overproduction of androgens and ovulatory dysfunction which lead to severe symptoms such as hirsutism, acne, insulin resistance, and infertility. Despite the frequency and disease burden of PCOS, its underlying causes remain unknown, and no causal therapeutic options are available. In recent years, several studies have shown that women with PCOS present with chronic low-grade inflammation indicating an overactivity of the pro-inflammatory cytokine interleukin-1 (IL-1). We show here how IL-1 might affect the ovarian physiology and pathophysiology in animals and humans by reviewing experimental studies on ovarian IL-1 system gene expression and on the effects of exogenous IL-1 on ovarian functions. Although IL-1 ligands and receptors are expressed within the ovarian cells, IL-1 seems to negatively affect the delicate balance between the sex hormones and dominant follicle development, as well as fertility. Whether blockade of the IL-1 signaling leads to an improvement of PCOS-related hormonal abnormalities and symptoms remains to be elucidated in future interventional studies

[Comorbidity in infertile couples]

Pregnancy is the result of a series of highly complex processes, which can be deranged by multiple disturbances on many different levels. Physicians are increasingly dealing with couples suffering from infertility. This rise in case numbers is mainly due to the fact that couples are more and more delaying childbearing until a later phase of their reproductive life, when their social and professional careers are established. The increasing mean age at the first birth has a negative impact on fertility by deteriorating quality and reducing the quantity of oocytes. With increasing age systemic diseases are becoming more coincidental, which in turn tend to exert negative effects on fecundity and fertility both in males and females. This review highlights some associations between infertility and various common systemic diseases. Both general practitioners and gynecologists should counsel young women about the finity of the reproductive phase of their life. Young couples are to be informed, that a "healthy lifestyle" without smoking, sexual transmitted diseases and without metabolic diseases as diabetes and obesity can have a positive effect not only on their general health but also on their fertility and the outcome of future pregnancies

Does prior hysteroscopy affect pregnancy outcome in primigravid infertile women?

OBJECTIVE: An increasing proportion of infertile women are subjected to hysteroscopy. The effect of hysteroscopy on the pregnancy rate in assisted reproduction has been demonstrated to be favorable, but cervical dilation in the course of hysteroscopy may have an adverse effect on pregnancy outcome. We sought to investigate the effect of hysteroscopy on the risk of early miscarriage, preterm delivery, low birthweight, and other complications of pregnancy. STUDY DESIGN: This was a longitudinal retrospective cohort study at a university hospital. Data of 654 first-time singleton pregnancies between January 1997 and March 2011 in women with primary infertility were retrieved from a prospective data collection. Four cohorts were constructed based on exposure to hysteroscopy and pregnancy outcome (early miscarriage vs live birth). The primary endpoint was the duration of pregnancy at 37 weeks. Pregnancy outcomes of 167 infertile patients exposed to cervical dilation and hysteroscopy were compared with those of 327 infertile women unexposed to hysteroscopy. RESULTS: The incidence of miscarriage, preterm birth, placenta previa, and premature rupture of membranes after maternal exposure to hysteroscopy was similar to that in women not exposed. CONCLUSION: Prior hysteroscopy in infertile women does not affect subsequent pregnancy outcome