Unexplained infertility is defined as the absence of conception despite 12 months of unprotected intercourse, not explained by anovulation, poor sperm quality, tubal pathology or any known cause of infertility. The two most applied treatments for unexplained infertility are intra-uterine insemination and in vitro fertilisation. As these treatments do not target a specific mechanism but rather increase the probability of conception as compared to natural conception chances, they should be weighed against the prognosis of natural conception. The use of prognostic models could facilitate in identifying who benefits from treatment and who can delay treatment for 6 months, thus aiming for natural conception. This is important, as treatments can have side effects for the woman and her offspring, and their cost may jeopardise access to care.

Polycystic ovary syndrome (PCOS) presents with a spectrum of conditions resulting from androgen excess, anovulation and metabolic syndrome. Patients with PCOS may see their primary care physicians for various presentations, including hirsutism, acne, menstrual irregularities, infertility, obesity, and psychiatric disorders such as anxiety and depression. Management of these patients should include screening for Type 2 diabetes mellitus, dyslipidaemia and hypertension. Treatment should be targeted to each patient's phenotype and personal expectations such as desire for pregnancy. Psychological well-being due to the effects on physical appearance is also an important consideration. Diet and exercise are major components in the management of patients with PCOS and obesity. The first-line therapy for fertility and metabolic syndrome in PCOS is lifestyle modification with diet and exercise, followed by pharmacological therapy.

Does starting IUI with ovarian stimulation (IUI-OS) within 1.5 years after completion of the fertility workup increase ongoing pregnancy rates compared to expectant management in couples with unexplained subfertility?

Ovulation is triggered by gonadotropin surge-induced signaling cascades. To study the role of extracellular signal-regulated kinase 1/2 (ERK1/2) in bovine ovulation, we administered the pharmacological inhibitor, PD0325901, into the preovulatory dominant follicle by intrafollicular injection. Four of five cows treated with 50 µM PD0325901 failed to ovulate. To uncover the molecular basis of anovulation in ERK1/2-inhibited cows, we collected granulosa and theca cells from Vehicle and PD0325901 treated follicles. Next-generation sequencing of granulosa cell RNA revealed 285 differentially expressed genes between Vehicle and PD0325901-treated granulosa cells at 6 h post-GnRH. Multiple inflammation-related pathways were enriched among the differentially expressed genes. The ERK1/2 dependent LH-induced genes in granulosa cells included EGR1, ADAMTS1, STAT3 and TNFAIP6. Surprisingly, PD0325901 treatment did not affect STAR expression in granulosa cells at 6 h post-GnRH. Granulosa cells had higher STAR protein and theca cells had higher levels of STAR mRNA in ERK1/2-inhibited follicles. Further, both granulosa and theca cells of ERK1/2-inhibited follicles had higher expression of SLC16A1, a monocarboxylate transporter, transporting substances including β-hydroxybutyrate across the plasma membrane. Taken together, ERK1/2 plays a significant role in mediating LH surge-induced gene expression in granulosa and theca cells of the ovulating follicle in cattle.

How well does a previously developed dynamic prediction model perform in an external, geographical validation in terms of predicting the chances of natural conception at various points in time?

Polycystic ovary syndrome (PCOS) affects 6-10% of women and could be considered one of the most common endocrine alterations in women of reproductive age. The syndrome is characterized by several hormonal and metabolic alterations, including insulin resistance and hyperandrogenism, which play a severe detrimental role in the patient's fertility. We aimed to offer an overview about drug metabolism in the PCOS population. Nevertheless, we did not find any study that directly compared drug metabolism between PCOS and healthy women. We therefore decided to summarize briefly how hormonal and insulin sensitizer drugs act differently in healthy and PCOS women, who show altered steroidogenesis by theca cells and metabolic imbalance, focusing especially on assisted reproductive techniques. To date, data about drug metabolism in the PCOS population appears to be extremely limited. This important gap could have significant implications for therapeutic approaches and future perspectives: the dosage of drugs commonly used for the treatment of PCOS women should be tailored according to each patient's characteristics; we should implement new clinical trials in order to identify the best pharmacologic strategy for PCOS patients undergoing in vitro fertilization (IVF); it would be advisable to create an international expert panel to investigate the drug metabolism in the PCOS population.