Search Results (20)

Background: Does maternal body mass index (BMI) influence embryo morphokinetics in fresh embryo transfer cycles, and how does this relate to clinical outcomes and obstetric complications? Methods: A retrospective cohort study was conducted on 2238 fresh embryo transfer (ET) cycles, categorized into four BMI groups: underweight, normal weight, overweight, and obese. Baseline characteristics, stimulation parameters, hormonal profiles, morphokinetic data, and pregnancy and delivery outcomes were analyzed. Results: Higher BMI was associated with more anovulatory infertility and greater endometrial thickness. Peak estradiol and estradiol-to-oocyte ratios declined progressively with increasing BMI, despite preserved oocyte yield and embryo quality scores. Interestingly, the underweight group exhibited a significantly distinct biphasic morphokinetics developmental pattern compared with the overweight and obese groups. Pregnancy rates, including clinical and live birth, did not differ significantly across BMI groups. However, obese women had markedly higher cesarean section rates (51.9% vs. ~25–28% in other groups) and a non-significant trend toward more gestational diabetes. Other perinatal outcomes, such as preeclampsia and preterm birth, were not significantly different. Conclusions: In fresh IVF cycles, a higher BMI does not impair pregnancy achievement but is linked to altered hormonal response and increased obstetric risk, particularly cesarean delivery. These findings highlight the importance of preconception counseling and targeted obstetric management for women with elevated BMI undergoing fresh ET. Full article

Background: Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility. The apoptosis of granulosa cells (GCs) is strongly associated with the impaired follicular development in PCOS. The underlying mechanisms, however, remain incompletely elucidated. A significant increase in circulating lactic acid, an anaerobic respiration product, has been detected in PCOS patients. Yet, alterations in local ovarian lactic acid levels and their impact on GCs remain unknown. Methods: PCOS mouse models were established via 20-day daily subcutaneous dehydroepiandrosterone (DHEA) injections. In vitro experiments utilized DHEA-treated KGN cells to mimic hyperandrogenic conditions. Circulating, ovarian, and cellular lactic acid concentrations were quantified. Intracellular and extracellular pH values were measured using BCECF-AM fluorescent probe and a blood gas analyzer, respectively. Apoptosis was assessed through both flow cytometry and TUNEL assay. The antioxidant N-acetylcysteine (NAC) was used to investigate its effects on lactic acid levels and the subsequent GC apoptosis. Results: High androgen levels caused mitochondrial damage, promoted anaerobic glycolysis and led to lactic acid accumulation, inducing decreased intracellular pH and thus apoptosis of GCs. The antioxidant NAC effectively alleviated oxidative stress, mitigated mitochondrial damage, and decreased lactic acid levels and apoptosis in KGN cells. In PCOS mice, NAC improved ovarian morphology, but it did not affect the estrous cycle of the mice. Conclusions: Hyperandrogenemia-induced mitochondrial dysfunction caused the accumulation of lactic acid and thus apoptosis of ovarian GCs in PCOS mice. NAC enhanced mitochondrial function, consequently decreasing lactic acid concentrations. These findings suggest novel therapeutic targets for PCOS. Full article

Ovarian aging is characterized by a gradual decline in both reproductive and endocrine functions, ultimately culminating in the cessation of ovarian activity around the age of 50, when most women experience natural menopause. The decline begins early, as follicular attrition is initiated in utero and continues throughout childhood and reproductive life. Most follicles undergo atresia without progressing through substantial stages of growth. With increasing age, a pronounced reduction occurs in the population of resting follicles within the ovarian reserve, accompanied by a decline in the size of growing follicular cohorts. Around the age of 38, the rate of follicular depletion accelerates, sometimes resulting in diminished ovarian reserve (DOR). The subsequent menopausal transition involves complex, irregular hormonal dynamics, manifesting as increasingly erratic menstrual patterns, primarily driven by fluctuations in circulating estrogens and a rising incidence of anovulatory cycles. In parallel with the progressive depletion of the follicular pool, the serum concentrations of anti-Müllerian hormone (AMH) decline gradually, while reductions in inhibin B levels become more apparent during the late reproductive years. The concomitant decline in both inhibin B and estrogen levels leads to a compensatory rise in circulating follicle-stimulating hormone (FSH) concentrations. Together, these endocrine changes, alongside the eventual exhaustion of the follicular reserve, converge in the onset of menopause, which is defined by the absence of menstruation for twelve consecutive months. The mechanisms contributing to ovarian aging are complex and multifactorial, involving both the oocyte and the somatic cells within the follicular microenvironment. Oxidative stress is thought to play a central role in the age-related decline in oocyte quality, primarily through its harmful effects on mitochondrial DNA integrity and broader aspects of cellular function. Although granulosa cells appear to be relatively more resilient, they are not exempt from age-associated damage, which may impair their hormonal activity and, given their close functional relationship with the oocyte, negatively influence oocyte competence. In addition, histological changes in the ovarian stroma, such as fibrosis and heightened inflammatory responses, are believed to further contribute to the progressive deterioration of ovarian function. A deeper understanding of the biological processes driving ovarian aging has facilitated the development of experimental interventions aimed at extending ovarian functionality. Among these are the autologous transfer of mitochondria and stem cell-based therapies, including the use of exosome-producing cells. Additional approaches involve targeting longevity pathways, such as those modulated by caloric restriction, or employing pharmacological agents with geroprotective properties. While these strategies are supported by compelling experimental data, robust clinical evidence in humans remains limited. Full article

Background/Objectives: Both hyperandrogenism (HA) and vitamin D deficiency (VDD) can separately lead to impaired vascular reactivity and ovulatory dysfunction in fertile females. The aim was to examine the early interactions of these states in a rat model of PCOS. Methods: Four-week-old adolescent female rats were divided into four groups: vitamin D (VD)-supplemented (n = 12); VD-supplemented and testosterone-treated (n = 12); VDD- (n = 11) and VDD-and-testosterone-treated (n = 11). Animals underwent transdermal testosterone treatment for 8 weeks. Target VD levels were achieved with oral VD supplementation and a VD-free diet. Estrous cycles were followed by vaginal smear, and quantitative histomorphometric measurements of the ovaries were also taken. In the 8th week, testosterone- and estrogen-induced relaxation of coronary arterioles was examined with pressure angiography. Estrogen receptor (ER) density and oxidative and nitrative stress parameters (Poly-(ADP-Ribose)-Polymerase and 3-nitrotyrosine) in the vessel wall were investigated with immunohistochemistry. Results: VDD caused impaired estrous cycles, and testosterone caused anovulatory cycles (the cycles were stopped at the diestrous phase). VDD combined with testosterone treatment resulted in reduced testosterone and estrogen vasorelaxation, lower ER density, and higher oxidative and nitrative stress in the vessel wall. Conclusions: PCOS with vitamin D deficiency may be associated with increased oxidative–nitrative stress in coronary arterioles. This oxidative and nitrative stress, potentially caused by hyperandrogenism and/or vitamin D deficiency, could impair estrogen-induced relaxation of the coronary arterioles, possibly by decreasing NO bioavailability and disrupting the estrogen-induced relaxation pathway. Full article

Background: Adolescence is the period of life between the ages of 10 and 19. This period is essentially dominated by puberty. The first menstruation, called menarche, occurs, on average, at the age of 12–13. The period after menarche, especially the first 2 years, is characterized by anovulatory cycles, which can be accompanied by menstrual irregularities. This review aims to describe the current status of the diagnostic and therapeutic challenges of the physiological and pathological causes of menstrual irregularities in adolescence and evaluates the benefits from interdisciplinary collaboration to ensure optimal care. Methods: A systematic literature search was conducted in the PubMed database in April 2024 using the following term: “menstrual disorder adolescence”. A total of 1724 abstracts were screened, and relevant articles from the last 10 years were included. In addition, a supplementary topic-relevant literature search of the guidelines of the European Society of Human Reproduction and Embryology (ESHRE) and the guidelines of the Arbeitsgemeinschaft der wissenschaftlichen medizinischen Fachgesellschaft (awmf) was carried out. Results: In addition to cycle irregularities that occur physiologically as a result of anovulatory cycles in the context of the immaturity of the hypothalamic–pituitary–gonadal axis, there are other cycle abnormalities that can be classified as pathological and need to be recognized and treated. Conclusions: Increasing awareness of the various specialist disciplines of physiological and pathological cycle abnormalities in adolescence and interdisciplinary cooperation between them can have a positive influence on the quality of life of adolescent women with cycle abnormalities. Full article

Background/Objectives: Infertility constitutes a significant challenge for couples around the world. Ovarian dysfunction, a major cause of infertility, can manifest with anovulatory cycles, elevated follicle-stimulating hormone levels, and diminished ovarian reserve markers such as anti-Müllerian hormone (AMH) levels or the Antral Follicle Count (AFC). Blood-derived therapies including platelet-rich plasma (PRP) have been used in fertility treatments in women with low ovarian reserve or premature ovarian insufficiency. This prospective clinical cohort study aims to assess the effects of intraovarian PRP therapy on ovarian function in women diagnosed with anovulatory cycles. Methods: The preliminary findings of this prospective cohort study are based on the first 32 patients enrolled. In this study, patients over 40 years old with anovulatory infertility were included. Venous blood samples were collected from each participant for the preparation of autologous platelet-rich plasma (PRP). Each participant received two courses of intraovarian PRP injections using a transvaginal ultrasound-guided approach. Serum levels of reproductive hormones before and after PRP intervention were measured. Results: This study’s results demonstrate a significant improvement in ovarian physiology following transvaginal ultrasound-guided PRP infusion. A 75% increase in Antral Follicle Count (AFC) was observed, which was statistically significant. Furthermore, statistically significant reductions in follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin levels were observed. Serum Vitamin D 1–25 levels were substantially increased after the injection. Conclusions: These findings highlight the beneficial impact of intraovarian PRP injection in optimizing ovarian function and other metabolic parameters. However, the published literature on this subject is limited and further clinical studies should be conducted to confirm the role of intraovarian PRP in fertility treatments. Full article

Research question: Clomiphene citrate (CC) is one of the first-line treatments for ovulation induction in women with anovulatory polycystic ovary syndrome (PCOS). However, nearly 1 out of 2 women is resistant to 50 mg/day of CC. The objective of this study is to investigate the clinical, biological, and/or ultrasound factors that may predict the resistance to 50 mg/day of CC in the first cycle of treatment in women with anovulatory PCOS. This would make it possible to identify PCOS patients to whom the dose of 100 mg/day would be offered as of the first cycle. Design: A retrospective and monocentric study was conducted on 283 women with anovulatory PCOS who required the use of ovulation induction with CC (903 cycles). Results: During the first cycle of treatment, 104 patients (36.8%) were resistant to 50 mg/day of CC. Univariate regression analysis showed that patients who resisted 50 mg/day of CC had significantly higher BMI, waist circumference, serum levels of AMH, total testosterone, Δ4-androstenedione, 17-OHP, and insulin (p < 0.05), compared to patients ovulating with this dose. Serum levels of SHBG were significantly lower in patients resistant to 50 mg/day (p < 0.05). After multivariate analysis, only AMH and SHBG remained statistically significant (p = 0.01 and p = 0.001, respectively). However, areas under the ROC curves were weak (0.59 and 0.68, respectively). Conclusion: AMH and SHBG are the only two parameters significantly associated with the risk of resistance to 50 mg/day of CC. However, no satisfactory thresholds have been established to predict resistance to 50 mg CC. Full article

Despite the beneficial effect of myo-inositol on metabolic, hormonal, and reproductive parameters of polycystic ovary syndrome (PCOS) patients, 28% to 38% could be resistant to this treatment. The combination with the milk protein α-lactalbumin can be a useful therapeutic approach to overcome inositol resistance and achieve ovulation in these women. This open-label prospective study aimed to compare the effects of supplementing myo-inositol plus α-lactalbumin vs myo-inositol alone on reproductive and metabolic abnormalities in PCOS. A total of 50 anovulatory women with a PCOS diagnosis were randomly assigned to receive myo-inositol alone or a combination of myo-inositol and α-lactalbumin for three months. Anthropometric measures, hormonal levels, and menstrual cycle duration were collected at baseline and after treatment. The therapy with myo-inositol plus α-lactalbumin improved both ovulation rate and menstrual cycle duration more than myo-inositol alone. The body weight was significantly reduced in women receiving myo-inositol plus α-lactalbumin, while patients in the myo-inositol group experienced no change. In addition, the improvement of hyperandrogenism was more prominent in patients treated with myo-inositol plus α-lactalbumin. The benefits of associating myo-inositol and α-lactalbumin clearly make this combination a true edge in the management of PCOS. Full article

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. Absent, impaired, or rare ovulation induces progesterone deficiency in the luteal phase, which is a critical problem in PCOS. A usual pattern of progesterone administration from a fixed and arbitrary pre-determined day of a menstrual cycle may preserve infertility but can easily be avoided. We present the case of a 29-year-old infertile woman who had been ineffectively treated for over two years. We introduced a line of therapy that was suited to her individual menstrual cycle by implementing biomarker recording. Supplementation based on a standardized observation of the basal body temperature (BBT) and cervical mucus stopped the vicious circle of absent ovulation and hyperandrogenism, restoring regular bleeding, ovulation cycles, and fertility. The implementation of a reliable fertility awareness method (FAM), accompanied by a standardized teaching methodology and periodic review of the observations recorded by the patient, validated through an ultrasound examination and plasma gonadotropins, estrogens, and progesterone concentrations, is key to achieving therapeutic success. The presented case is an example of a clinical vignette for many patients who have successfully managed to improve their fertility and pregnancy outcomes by applying the principles of a personalized treatment approach together with gestagens by recording their fertility biomarkers. Full article

The study objectives were to determine whether ovarian morphology can distinguish between women with regular menstrual cycles, normo-androgenic anovulation (NA-Anov), and PCOS and whether body mass index (BMI)-specific thresholds improved diagnostic potential. Women with PCOS (biochemical and/or clinical hyperandrogenism and irregular cycles; N = 66), NA-Anov (irregular cycles without clinical and/or biochemical hyperandrogenism; N = 64), or regular cycles (controls; cycles every 21–35 days in the absence of clinical or biochemical hyperandrogenism; N = 51) were evaluated. Participants underwent a reproductive history, physical exam, transvaginal ultrasound, and a fasting blood sample. Linear regression analyses were used to assess the impact of BMI on ovarian morphology across groups. The diagnostic performance of ovarian morphology for anovulatory conditions, and by BMI (lean: <25 kg/m²; overweight: ≥25 kg/m²), was tested using Receiver Operating Characteristic (ROC) curves. Follicle number per ovary (FNPO) and ovarian volume (OV), but not follicle number per cross-section (FNPS), increased across controls, NA-Anov, and PCOS. Overall, FNPO had the best diagnostic performance for PCOS versus controls (AUC_ROC = 0.815) and NA-Anov and controls (AUC_ROC = 0.704), and OV to differentiate between PCOS and NA-Anov (AUC_ROC = 0.698). In lean women, FNPO best differentiated between PCOS and controls (AUC_ROC = 0.843) and PCOS versus NA-Anov (AUC_ROC = 0.710). FNPS better distinguished between NA-Anov and controls (AUC_ROC = 0.687), although diagnostic performance was lower than when thresholds were generated using all participants. In women with overweight and obesity, OV persisted as the best diagnostic feature across all analyses (PCOS versus control, AUC_ROC = 0.885; PCOS versus NA-Anov, AUC_ROC = 0.673; NA-Anov versus controls, AUC_ROC = 0.754). Ovarian morphology holds diagnostic potential to distinguish between NA-Anov and PCOS, with marginal differences in diagnostic potential when participants were stratified by BMI suggesting that follicle number may provide better diagnostic performance in lean women and ovarian size in those with overweight. Full article

Several new quantitative fertility monitors are now available for at-home use that measure estrogen, luteinizing hormone (LH), and progesterone (PDG) in urine. This case report compares the Mira and Inito quantitative fertility monitors with the well-established qualitative ClearBlue fertility monitor. Three clinical scenarios were evaluated: a normal cycle, a prolonged luteinization cycle, and an anovulatory cycle. The identification of the luteal phase (or lack thereof in the case of anovulation) and the transition through the three processes of luteinization, progestation, and luteolysis were clearly demarcated with the help of quantitative LH and PDG. Quantitative fertility monitors have the potential to identify details of the luteal phase to help women with regular cycles and abnormal luteal phases to help target interventions for optimizing fertility. Full article

It is well known that a subgroup of women with PCOS present an excessive adrenal androgen production, generally associated with ovarian hyperandrogenism. In the past, it has been impossible to correlate adrenal hyperandrogenism to any clinical or hormonal pattern of PCOS. However, adrenal androgens are strictly dependent on age and their blood values reduce by 40% in patients moving from their twenties to thirties. Due to this, serum DHEAS values are strongly influenced by the age distribution of studied populations. To avoid this bias, in this study we retrospectively analyzed the clinical and hormonal data of PCOS women in their twenties (age between 20 and 29 years). Data of 648 young hyperandrogenic women with PCOS were evaluated. Serum DHEAS was increased in a third (33%) of studied patients and was associated with higher values of testosterone (T) and androstenedione (A). In each phenotype, patients with high DHEAS had higher values of T and A than patients with normal DHEAS of the same phenotype. Therefore, a DHEAS increase is generally part of a generalized higher androgen production in a subgroup of PCOS patients, independently of the finding of anovulatory or ovulatory cycles or of polycystic or normal ovaries. However, our study showed some important differences between PCOS phenotypes. A lower prevalence of increased DHEAS in A phenotype PCOS patients who generally have the highest androgen levels, versus non-classic (B or C) PCOS phenotypes, was observed. It was also found that patients with A phenotype PCOS present significantly lower BMI and serum insulin than patients with normal DHEAS of the same phenotype while, in patients with the B or C phenotype, the opposite occurs. We conclude that adrenal hyperandrogenism is more common in patients with non-classic (B and C) phenotypes of PCOS and is generally part of a generalized higher production of androgens in a subgroup of PCOS patients. However, other factors may increase the adrenal androgen production and influence the clinical expression of the syndrome. More studies in large, selected for age, populations of PCOS women with different phenotypes are needed. Full article

Background and objectives: Kisspeptin, also named metastin, showed important roles in initiating the secretion of gonadotropin-releasing hormone (GnRH) and is an essential factor in the development of polycystic ovaries syndrome (PCOS). Several research studies noticed associations between kisspeptin levels and patients with anovulatory cycles due to PCOS with an increased LH/FSH ratio. The aim of our study was to bring scientific evidence regarding the correlation between high kisspeptin and luteinizing hormone values in subfertile women due to PCOS. Materials and Methods: A prospective case-control study was conducted in “Elena Doamna” Hospital of Obstetrics and Gynecology between 4 January 2021 and 1 March 2022. All patients agreed to participate in our study, had ages between 18 and 45 years old, and had a body mass index between 18.5 and 30 kg/m². The study group consisted of subfertile patients with PCOS and menstrual disturbances, including amenorrhea or oligomenorrhea. The control group consisted of healthy patients with ovulatory cycles and no other reproductive or endocrinology pathologies. During the follicular phase of their menstrual cycle, patients had blood samples taken with the dosage of kisspeptin, LH, FSH, estradiol, insulin, glycemic levels, testosterone, and prolactin. Pelvic ultrasounds and clinical examinations were performed as well. Results: Significant differences were observed in kisspeptin, LH, FSH, and estradiol levels between patients with PCOS and the control group. After the univariate analysis, PCOS was significantly associated with increased kisspeptin, increased LH, and decreased FSH. There was no significant association between PCOS, estradiol, prolactin, and insulin. Conclusions: kisspeptin serum values are higher in subfertile PCOS patients, supporting the hypothesis that an over-stimulation of the KISS1 system might cause the hyper-stimulation of the HPG-axis. Full article

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women and a major cause of anovulatory infertility. A diagnosis of PCOS is established based the presence of two out of three clinical symptoms, which are criteria accepted by the ESHRE/ASRM (European Society of Human Reproduction and Embryology/American Society for Reproductive Medicine). Gonadotropin-releasing hormone (GnRH) is responsible for the release of luteinizing hormone, and follicle stimulating hormone from the pituitary and contributes a leading role in controlling reproductive function in humans. The goal of this review is to present the current knowledge on neuroendocrine determinations of PCOS. The role of such neurohormones as GnRH, and neuropeptides kisspeptin, neurokinin B, phoenixin-14, and galanin is discussed in this aspect. Additionally, different neurotransmitters (gamma-aminobutyric acid (GABA), glutamate, serotonin, dopamine, and acetylcholine) can also be involved in neuroendocrine etiopathogenesis of PCOS. Studies have shown a persistent rapid GnRH pulse frequency in women with PCOS present during the whole ovulatory cycle. Other studies have proved that patients with PCOS are characterized by higher serum kisspeptin levels. The observations of elevated serum kisspeptin levels in PCOS correspond with the hypothesis that overactivity in the kisspeptin system is responsible for hypothalamic-pituitary-gonadal axis overactivity. In turn, this causes menstrual disorders, hyperandrogenemia and hyperandrogenism. Moreover, abnormal regulation of Neurokinin B (NKB) is also suspected of contributing to PCOS development, while NKB antagonists are used in the treatment of PCOS leading to reduction in Luteinizing hormone (LH) concentration and total testosterone concentration. GnRH secretion is regulated not only by kisspeptin and neurokinin B, but also by other neurohormones, such as phoenixin-14, galanin, and Glucagon-like peptide-1 (GLP-1), that have favorable effects in counteracting the progress of PCOS. A similar process is associated with the neurotransmitters such as GABA, glutamate, serotonin, dopamine, and acetylcholine, as well as the opioid system, which may interfere with secretion of GnRH, and therefore, influence the development and severity of symptoms in PCOS patients. Additional studies are required to explain entire, real mechanisms responsible for PCOS neuroendocrine background. Full article

(1) Background: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility and endocrine disorders among women of reproductive age. Previous studies have employed lifestyle interventions to manage anovulatory infertility and endocrine disorders. However, the effect of lifestyle interventions on the metabolic index remains ambiguous; (2) Methods: Data were obtained through a systematic search of the Ovid-Medline, Ovid-EMBASE, and Cochrane Library databases. Two reviewers independently reviewed the literature in two stages. A consensus was achieved through discussions regarding the final selection of the literature; (3) Results: This study observed that the group that underwent lifestyle modifications displayed significant improvement in reproductive function compared to the control group. Combination therapy with diet and exercise resulted in improved fasting insulin levels, compared to monotherapy with diet or exercise. Moreover, moderate weight loss (a minimum of 5%) resulted in an improved metabolic index. The subgroup analysis revealed that the group that underwent lifestyle modifications had a significantly higher number of patients with improved menstrual cycles, compared to the control groups; (4) Conclusions: Lifestyle modification using combination therapy is a promising therapeutic approach that can be employed in the management of PCOS patients with obesity. This scenario warrants further studies with larger sample sizes to develop ideal treatment protocols. Full article