This systematic review aimed to compare the clinical efficacy of tamoxifen with that of clomiphene citrate (CC) in anovulatory patients. The PubMed, EMBASE, and CNKI databases were searched up to October 2016 for literature comparing tamoxifen with CC in anovulatory women. The pooled risk ratios (RR) or standardized mean differences (SMD) with 95% confidence intervals (CIs) were subjected to statistical analysis. Twelve studies involving 1302 patients with 2030 ovulation-induction cycles were summarized. There were no statistically significant differences for the ovulation and pregnancy rates in the tamoxifen comparing to the CC group in the pooled analysis. However, in the subgroup of case-control studies, tamoxifen was identified to be associated with higher ovulation (RR = 1.28, 95% CI: 1.07, 1.54, I2 = 0.0%) and pregnancy rates (RR = 1.82, 95% CI: 1.09, 3.06, I2 = 0.0%) than CC. However, no differences were detected in the subgroup of RCTs, even after sensitivity analyses. In addition, no significant differences were found in endometrial thickness and miscarriage rate. Our study showed that there might be some distinctions in the efficacy of TMX and CC for ovulation and pregnancy rates. However, the exact efficacy was needed to be confirmed further.

Functional hypothalamic amenorrhea is a form of chronic anovulation not due to identifiable organic causes with adverse health consequences. A thorough history is paramount in the identification of women with this disorder as it is usually associated with lifestyle factors such as stress, weight loss, and excessive exercise. In this paper, recently published clinical guidelines are reviewed and a series of cases is presented that highlights diagnostic and therapeutic challenges encountered.

In ovarian cystic follicles, molecular changes in the growing follicle may have a local action and contribute to anovulation and cystic formation. One of the candidate molecules that affect the steroid and gonadotropin signaling systems of cystic follicles is lipopolysaccharide (LPS), a cell wall component of gram-negative bacteria. To examine the molecular characteristics of bovine cystic follicles, we analyzed LPS concentration in follicular fluid of cystic follicles, and the expression of LPS receptors and steroidogenesis-related genes in granulosa and theca cells. Cystic follicles were categorized as estradiol (E2)-active (EACF) and E2-inactive cystic follicle (EICF). Overall, LPS concentration in follicular fluid of EACF and EICF was higher compared with healthy preovulatory follicles (POF). Expression of luteinizing hormone receptor (LHR) in granulosa and thecal cells was decreased in EACF and EICF compared with POF. Expression of CYP19 in granulosa cells of EACF and EICF was lower than POF. High expression of StAR in granulosa and thecal cells was observed in EICF. In granulosa cells, the expression of TLR4 and TLR2 mRNA was higher in EICF than other follicles. By contrast, higher expression of TLR2 in thecal cells was observed in EICF. Thus, high LPS concentration in follicular fluid of cystic follicles may be associated with the regulation of expression of steroidogenesis-related genes in granulosa and theca cells. These finding revealed the molecular characteristics of bovine ovarian cysts and possible involvement of LPS in the pathology of cystic follicle diseases.

Thyroid hormones are vital for the proper functioning of the female reproductive system, since they modulate the metabolism and development of ovarian, uterine and placental tissues. Therefore, hypo- and hyperthyroidism may result in subfertility or infertility in both women and animals. Other well-documented sequelae of maternal thyroid dysfunctions include menstrual/estral irregularity, anovulation, abortion, preterm delivery, preeclampsia, intrauterine growth restriction, postpartum thyroiditis, and mental retardation in children. Several studies have been carried out involving prospective and retrospective studies of women with thyroid dysfunction, as well as in vivo and in vitro assays of hypo- and hyperthyroidism using experimental animal models and/or ovarian, uterine and placental cell culture. These studies have sought to elucidate the mechanisms by which thyroid hormones influence reproduction to better understand the physiology of the reproductive system and to provide better therapeutic tools for reproductive dysfunctions that originate from thyroid dysfunctions. Therefore, this review aims to summarize and update the available information related to the role of thyroid hormones in the morphophysiology of the ovary, uterus and placenta in women and animals and the effects of hypo- and hyperthyroidism on the female reproductive system.

Tetragonia tetragonioides (Pall.) Kuntze (TTK) is a medicinal plant traditionally used to treat various diseases such as diabetic, inflammatory, and female-related disorders. Polycystic ovary syndrome (PCOS) is a common endocrinological disorder in women of reproductive age, and hyperandrogenism is a prominent feature of PCOS resulting in anovulation and infertility. In this study, we investigated the effects of a TTK extract on androgen generation and regulation of steroidogenic enzymes in vitro and in vivo. Human adrenocortical NCI-H295R cells were used to assess the effects of TTK extract on production of dehydroepiandrosterone and testosterone, as well as the protein expression of steroidogenic enzymes. Further, a letrozole-induced PCOS rat model was used in vivo to assess whether dietary administration of TTK extract restores normal hormones and reduces PCOS symptoms. TTK extract significantly inhibited forskolin (FOR)-induced androgen production in NCI-H295R cells and serum luteinizing hormone, testosterone, and follicular cysts, but not estradiol, were reduced in letrozole-induced PCOS rats orally administered the TTK extract. In addition, TTK extract inhibits androgen biosynthesis through the ERK-CREB signaling pathway, which regulates CYP17A1 or HSD3B2 expression. TTK extract could be utilized for the prevention and treatment of hyperandrogenism and other types of PCOS.

The polycystic ovary (PCO) syndrome (PCOS) is the most common cause of anovulatory infertility in women and is associated with several clinical disorders. Despite the great amount of research in the area, mechanisms involved in the genesis of this syndrome remain poorly understood. In a recent issue of Clinical Science (vol. 132, issue 7, 759-776), Wang and colleagues, highlight the important role of overactivated C-type natriuretic peptide (CNP) and natriuretic peptide receptor 2 (CNP/NPR2) system in preventing oocyte maturation and ovulation in PCOS mice model induced by androgen. Dehydroepiandrosterone (DHEA) treatment caused anovulation, high levels of androgen and estrogen receptors (AR and ER) in the ovary, high expression of CNP and natriuretic peptide receptor 2 (NPR2) in granulosa cells (GC), and an increase in testosterone and estradiol (E2) levels in sera. The high level of CNP/NPR2 was associated with oocyte meiotic arrest and very low ovulation rate. Treatment with human chorionic gonadotropin (hCG) or inhibitors of AR or ER reduced the level of CNP/NPR2, which resulted in meiotic resumption and ovulation. The article provided important information for understanding the effect of ovarian steroids on control of oocyte maturation and fertility and highlighted CNP/NPR2 as a specific pathway that is potentially involved in the ovulatory disruption in PCOS.

Dyslipidaemia and hyperglycaemia are associated with ovarian failure and both have been related to hypothyroidism. Hypothyroidism promotes anovulation and ovarian cysts in women and reduces the size of follicles and the expression of aromatase in the ovary of rabbits. Considering that ovarian steroidogenesis and ovulation depend on lipid metabolism and signalling, the aim of the present study was to analyse the effect of hypothyroidism on the lipid content and expression of peroxisome proliferator-activated receptor (PPAR) δ in the ovary. Ovaries from female rabbits belonging to the control (n=7) and hypothyroid (n=7) groups were processed to measure total cholesterol (TC), triacylglycerol (TAG) and glycogen content, as well as to determine the presence of granules containing oxidized lipids (oxysterols and lipofuscin) and the relative expression of perilipin A (PLIN-A) and PPARδ. Hypothyroidism increased TC and glycogen content, but reduced TAG content in the ovary. This was accompanied by a reduction in the expression of PLIN-A in total and cytosolic extracts, changes in the presence of granules containing oxidative lipids and low PPARδ expression. The results of the present study suggest that hypothyroidism modifies the content and signalling of lipids in the ovary, possibly affecting follicle maturation. These results could improve our understanding of the association between hypothyroidism and infertility in females.