Higher live birth rate following transdermal testosterone pretreatment in poor responders: a systematic review and meta-analysis.

A systematic review and meta-analysis was performed aiming to identify good-quality randomized controlled trials (RCT) evaluating testosterone pretreatment in poor responders. Eight RCTs were analysed, evaluating 797 women. Transdermal testosterone gel was used in all studies, with a dose ranging from 10 to 12.5 mg/day for 10-56 days. The main outcome measure was achievement of pregnancy, expressed as clinical pregnancy or live birth. Testosterone pretreatment was associated with a significantly higher live birth (risk ratio [RR] 2.07, 95% confidence interval [CI] 1.09-3.92) and clinical pregnancy rate (RR 2.25, 95% CI 1.54-3.30), as well as a significant increase in the number of cumulus-oocyte complexes retrieved. Significantly fewer days to complete ovarian stimulation, a lower total dose of gonadotrophins, a lower cancellation rate due to poor ovarian response and a thicker endometrium on the day of triggering of final oocyte maturation were observed. No significant differences were observed in oestradiol concentration, the numbers of follicles ≥17 mm, metaphase II oocytes, two-pronuclear oocytes and embryos transferred, and the proportion of patients with embryo transfer. The current study suggests that the probability of pregnancy is increased in poor responders pretreated with transdermal testosterone who are undergoing ovarian stimulation for IVF.

Improvement in sperm quality by oral antioxidant supplementation in infertile men with varicocele who have not undergone surgical repair: Systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to assess whether oral antioxidant supplementation improves sperm quality in men with infertility and varicocele (VCL) who have not undergone surgical repair. In men with infertility and VCL who had not undergone surgical repair oral antioxidant supplementation significantly increased sperm concentration (WMD +5.86 × 106 /ml 95% CI: +1.47 to +10.24, p < 0.01; random effects model, six studies, 213 patients), total motility (WMD + 3.76%, 95% CI: +0.18 to +7.34, p = 0.04; random effects model, three studies, 93 patients), progressive motility (WMD + 6.38%, 95% CI: +3.04 to +9.71, p < 0.01; random effects model, three studies, 84 patients) and seminal volume (WMD +0.55 ml, 95%CI: +0.06 to +1.04, p = 0.03; random effects model, four studies, 120 patients). On the other hand, no significance difference was observed in sperm morphology (WMD +3.89%, 95% CI: -0.14 to +7.92, p = 0.06; random effects model, five studies, 187 patients). In conclusion, limited evidence suggests that the use of oral antioxidants in men with infertility and VCL, who have not undergone surgical repair improves their seminal volume, sperm concentration, total and progressive motility.

How frequent is severe ovarian hyperstimulation syndrome after GnRH agonist triggering in high-risk women? A systematic review and meta-analysis.

The aim of the present systematic review and meta-analysis was to assess the incidence of severe ovarian hyperstimulation syndrome (OHSS) after triggering of final oocyte maturation with gonadotrophin releasing hormone agonist (GnRHa) in high-risk women. The pooled incidence of severe OHSS in high-risk women who did not receive any form of luteal phase support was 0% (95% CI 0.0 to 0.0, I2 = 0%, random-effects model, 14 data sets, 983 women). The pooled incidence of severe OHSS in high-risk women in whom HCG was added to standard luteal phase support was 1% (95% CI 0.0 to 2.0, I2 = 27.02%, random-effects model, 10 data sets, 707 women). The incidence of severe OHSS in high-risk women triggered by a combination of GnRHa and HCG (dual triggering), who received standard luteal phase support, was 1% (95% CI 0.0 to 3.0, one study, 182 women). The incidence of severe OHSS in high-risk women, is not eliminated when HCG is administered either concomitantly with GnRHa (dual triggering), during the luteal phase after GnRHa triggering, or both. On the contrary, it is eliminated when no luteal support is administered.

Expression of genes that regulate follicle development and maturation during ovarian stimulation in poor responders.

RESEARCH QUESTION: Sex hormone-binding globulin (SHBG), androgen receptor (AR), LH beta polypeptide (LHB), progesterone receptor membrane component 1 (PGRMC1) and progesterone receptor membrane component 2 (PGRMC2) regulate follicle development and maturation. Their mRNA expression was assessed in peripheral blood mononuclear cells (PBMC) of normal and poor responders, during ovarian stimulation. DESIGN: Fifty-two normal responders and 15 poor responders according to the Bologna criteria were enrolled for IVF and intracytoplasmic sperm injection and stimulated with 200 IU of follitrophin alpha and gonadotrophin-releasing hormone antagonist. HCG was administered for final oocyte maturation. On days 1, 6 and 10 of stimulation, blood samples were obtained, serum hormone levels were measured, RNA was extracted from PBMC and real-time polymerase chain reaction was carried out to identify the mRNA levels. Relative mRNA expression of each gene was calculated by the comparative 2-DDCt method. RESULTS: Differences between mRNA levels of each gene on the same time point between the two groups were not significant. PGRMC1 and PGRMC2 mRNA levels were downregulated, adjusted for ovarian response and age. Positive correlations between PGRMC1 and AR (standardized beta = 0.890, P < 0.001) from day 1 to 6 and PGRMC1 and LHB (standardized beta = 0.806, P < 0.001) from day 1 to 10 were found in poor responders. PGRMC1 and PGRMC2 were positively correlated on days 6 and 10 in normal responders. CONCLUSIONS: PGRMC1 and PGRMC2 mRNA are significantly decreased during ovarian stimulation, with some potential differences between normal and poor responders.

Association between body mass index and oocyte maturation in patients triggered with GnRH agonist who are at high risk for severe ovarian hyperstimulation syndrome: an observational cohort study.

RESEARCH QUESTION: Is body-mass index (BMI) associated with oocyte maturation in women at high risk for developing severe ovarian hyperstimulation syndrome (OHSS) who are triggered with gonadotrophin releasing hormone (GnRH) agonist? DESIGN: Prospective observational cohort study. A total of 113 patients at high risk for severe OHSS (presence of at least 19 follicles ≥11 mm) pre-treated with gonadotrophin releasing hormone (GnRH) antagonists and recombinant FSH were administered 0.2 mg triptorelin to trigger final oocyte maturation. Patients were classified in two groups depending on their BMI: ΒΜΙ less than 25 kg/m2 (n = 72) and ΒΜΙ 25 kg/m2 or over (n = 41). Baseline, ovarian stimulation and embryological characteristics, as well as luteal-phase hormone profiles, were compared in patients classified into the two BMI groups. The main outcome measure was the number of mature oocytes. RESULTS: A significantly higher number of mature (metaphase II) oocytes (19 [18-21] versus 16 [13-20], P = 0.029) was present in women with BMI less than 25 kg/m2 compared with those with BMI 25 kg/m2 or greater. The number of retrieved oocytes, the number of fertilized oocytes, oocyte retrieval, maturation and fertilization rates were similar in the two groups. A significantly higher dose of recombinant FSH was required for patients with BMI 25 kg/m2 or greater compared with patients with BMI less than 25 kg/m2 (1875 [1650-2150] IU versus 1650 [1600-1750] IU, P = 0.003) and the two groups displayed different luteal phase hormonal profiles. CONCLUSIONS: Among women at high risk for developing severe OHSS who are triggered with a standard dose (0.2 mg) of the GnRH agonist triptorelin, women with BMI 25 kg/m2 or greater had significantly fewer mature oocytes, required a higher total dose of recombinant FSH compared with women with BMI less than 25 kg/m2.

Testicular versus ejaculated spermatozoa for ICSI in patients without azoospermia: A systematic review.

The use of testicular spermatozoa in men without azoospermia has been proposed as a means to increase the chances of pregnancy following assisted reproductive treatment. The purpose of this systematic review is to assess whether clinical outcomes are better when testicular rather than ejaculated spermatozoa are used for intracytoplasmic sperm injection in patients with abnormal semen parameters without azoospermia. A literature search identified four eligible studies out of 757 initially found. In a prospective study in men with high DNA fragmentation index (DFI) and oligozoospermia, the probability of live birth was significantly higher with testicular compared to ejaculated spermatozoa (risk ratio [RR]: 1.75, 95% confidence interval [CI]: 1.14-2.70). This was not the case in a retrospective study in men with high DFI only (RR: 2.36, 95% CI: 0.98-5.68). Clinical pregnancy rates were similar in a randomized controlled trial in men with asthenozoospermia with or without teratozoospermia (RR: 2.85, 95% CI: 0.76-10.69) and in a retrospective study in men with isolated asthenozoospermia (RR: 1.09, 95% CI: 0.56-2.14). Currently, there is limited, low-quality evidence suggesting that a higher probability of pregnancy might be expected using testicular rather than ejaculated spermatozoa, only in men with high DFI and oligozoospermia.

Basal serum progesterone and history of elevated progesterone on the day of hCG administration are significant predictors of late follicular progesterone elevation in GnRH antagonist IVF cycles.

STUDY QUESTION: Are there any baseline predictors of progesterone elevation (PE) on the day of human chorionic gonadotrophin (hCG) which are not associated with the intensity of ovarian stimulation in women undergoing in vitro fertilization (IVF) using follicle stimulating hormone (FSH) and gonadotrophin-releasing hormone (GnRH) antagonists? SUMMARY ANSWER: Basal (Day 2 of the menstrual cycle) serum progesterone concentration and history of PE are baseline variables that can predict the occurrence of PE on the day of hCG independently of the intensity of ovarian stimulation. WHAT IS KNOWN ALREADY: PE on the day of hCG is associated with the magnitude of the ovarian response to stimulation. For this reason, it has been hypothesized that milder ovarian stimulation might reduce the probability of PE. However, given the fact that the number of oocytes retrieved is associated with the probability of live birth, such a strategy should be considered only in patients that are at high risk of PE on the day of hCG. STUDY DESIGN, SIZE, DURATION: This is a retrospective analysis of a cohort of fresh IVF/ICSI cycles (n = 1702) performed in a single IVF centre during the period 2001-2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients in whom ovarian stimulation was performed with FSH and GnRH antagonists and with basal FSH <14.0 mIU/ml, progesterone (P) ≤1.6 ng/ml and estradiol (E2) ≤80 pg/ml on the same day (prior to the initiation of stimulation) were considered eligible. PE was defined as serum progesterone concentration >1.5 ng/ml. Pre-stimulation characteristics of patients and basal hormonal profile were assessed for their ability to predict the occurrence of PE after ovarian stimulation through generalized estimating equation univariable and multivariable regression analyses, controlling for the effect of ovarian stimulation. Furthermore, a secondary analysis in a subset of patients with multiple IVF cycles explored whether the occurrence of PE in one of the previous cycles included in this study is associated with a significantly higher occurrence of PE elevation in subsequent cycles. MAIN RESULTS AND THE ROLE OF CHANCE: Univariable regression analyses showed that female age (OR: 0.97; 95% CI: 0.94-0.99), basal FSH (OR: 0.85; 95% CI: 0.79-0.92) and basal P (OR: 4.20; 95% CI: 2.47-7.12) were baseline variables that could significantly predict PE on the day of hCG. When these variables were entered in the same model as covariates, only basal FSH (OR: 0.86; 95% CI: 0.80-0.94) and basal P (OR: 3.83; 95% CI: 2.24-6.56) could still predict the occurrence of PE. Basal P (OR: 6.30; 95% CI: 3.35-11.82) was the only variable that could significantly predict the occurrence of PE on the day of hCG after adjusting for the intensity of ovarian stimulation. The secondary analysis revealed that history of PE on the day of hCG in a previous cycle was also strongly associated with an increased risk of PE in a subsequent cycle. LIMITATIONS, REASONS FOR CAUTION: This is a retrospective analysis and although the effect of the most important confounders was controlled for in the multivariable analysis, the presence of residual bias cannot be excluded. WIDER IMPLICATIONS OF THE FINDINGS: The findings of this study might help clinicians identify patients at high risk for late follicular PE and alter the management of their cycle. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: Not applicable.

Estimating the net effect of progesterone elevation on the day of hCG on live birth rates after IVF: a cohort analysis of 3296 IVF cycles.

STUDY QUESTION: What is the proper way of assessing the effect of progesterone elevation (PE) on the day of hCG on live birth in women undergoing fresh embryo transfer after in vitro fertilization (IVF) using GnRH analogues and gonadotrophins? SUMMARY ANSWER: This study indicates that a multivariable approach, where the effect of the most important confounders is controlled for, can lead to markedly different results regarding the association between PE on the day of hCG and live birth rates after IVF when compared with the bivariate analysis that has been typically used in the relevant literature up to date. WHAT IS KNOWN ALREADY: PE on the day of hCG is associated with decreased pregnancy rates in fresh IVF cycles. Evidence for this comes from observational studies that mostly failed to control for potential confounders. STUDY DESIGN, SIZE, DURATION: This is a retrospective analysis of a cohort of fresh IVF/intracytoplasmic sperm injection cycles (n = 3296) performed in a single IVF centre during the period 2001-2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients in whom ovarian stimulation was performed with gonadotrophins and GnRH analogues. Natural cycles and cycles where stimulation involved the administration of clomiphene were excluded. In order to reflect routine clinical practice, no other exclusion criteria were imposed on this dataset. The primary outcome measure for this study was live birth defined as the delivery of a live infant after 24 weeks of gestation. We compared the association between PE on the day of hCG (defined as P > 1.5 ng/ml) and live birth rates calculated by simple bivariate analyses with that derived from multivariable logistic regression. The multivariable analysis controlled for female age, number of oocytes retrieved, number of embryos transferred, developmental stage of embryos at transfer (cleavage versus blastocyst), whether at least one good-quality embryo was transferred, the woman's body mass index, the total dose of FSH administered during ovarian stimulation and the type of GnRH analogues used (agonists versus antagonists) during ovarian stimulation. In addition, an interaction analysis was performed in order to assess whether the ovarian response (<6, 6-18, >18 oocytes) has a moderating effect on the association of PE on the day of hCG with live birth rates after IVF. MAIN RESULTS AND THE ROLE OF CHANCE: Live birth rates were not significantly different between cycles with and those without PE when a bivariate analysis was performed [odds ratio (OR): 0.78, 95% confidence interval (CI): 0.56-1.09]. However, when a multivariable analysis was performed, controlling for the effect of the aforementioned confounders, live birth rates (OR: 0.68, 95% CI: 0.48-0.97) were significantly decreased in the group with PE on the day of hCG. The number of oocytes retrieved was the most potent confounder, causing a 29.4% reduction in the OR for live birth between the two groups compared. Furthermore, a moderating effect of ovarian response on the association between PE and live birth rates was not supported in the present analysis since no interaction was detected between PE and the type of ovarian response (<6, 6-18, >18 oocytes). LIMITATIONS, REASONS FOR CAUTION: This is a retrospective analysis of data collected during a 12-year period, and although the effect of the most important confounders was controlled for in the multivariable analysis, the presence of residual bias cannot be excluded. WIDER IMPLICATIONS OF THE FINDINGS: This analysis highlights the need for a multivariable approach when researchers or clinicians aim to evaluate the impact of PE on pregnancy rates in their own clinical setting. Failure to do so might explain why many past studies have failed to identify the detrimental effect of PE in fresh IVF cycles. STUDY FUNDING/COMPETING INTERESTS: None.

Propofol versus thiopental sodium as anaesthetic agents for oocyte retrieval: a randomized controlled trial.

Clinical outcomes of IVF cycles using propofol or thiopental sodium as anaesthetic agents for oocyte retrieval were compared. The primary outcome measure was fertilization rate per patient. One hundred and eighty patients undergoing ovarian stimulation with gonadotrophins and gonadotrophin-releasing hormone antagonists for IVF were randomized to receive either propofol (n = 90) or thiopental sodium (n = 90). No significant differences in baseline characteristics were present between the two groups. Overall fertilization rates were similar between propofol and thiopental sodium groups, respectively: median (IQR): 54.8 (29.2) versus 54.6 (29.7); fertilization rates for intracytoplasmic sperm injection only: median (IQR): 70 (50) versus 75 (50), respectively. For secondary outcome measures, time under anaesthesia was significantly increased in the thiopental sodium group: median (IQR): 12(5) versus 10 (4.5) min, P = 0.019 compared with the propofol group. Number of cumulus oocyte complexes retrieved [median (IQR): 7.1 (6.3) versus 6.5 (5.6)] did not differ significantly between the two groups. A non-significant difference in live birth rates per randomized patient of +4.4% (95% CI: -5.7 to +14.6) in favour of propofol was observed. Use of propofol compared with thiopental sodium for general anaesthesia during oocyte retrieval results in similar fertilization rates and IVF outcomes.

Is the time interval between HCG administration and oocyte retrieval associated with oocyte retrieval rate?

The aim of this study was to evaluate whether prolongation of the time interval between HCG administration and oocyte retrieval, from 36 h to 38 h, affects oocyte retrieval rate in women undergoing ovarian stimulation with gonadotrophins and GnRH antagonists for IVF. One hundred and fifty-six normo-ovulatory women were randomized to have oocyte retrieval performed 36 h (n = 78) or 38 h (n = 78) following HCG administration. Oocyte retrieval rate was defined as number of cumulus-oocyte-complex (COC) retrieved/follicle ≥ 11 mm present on day of HCG administration. No significant differences were observed between the groups regarding baseline characteristics. Moreover, no significant difference was observed between the groups regarding oocyte retrieval rate (difference: + 1.2%, 95% CI for difference between medians: -4.5 to +12.1). The median (95% CI for the median) was not significantly different between the groups regarding number of cumulus-oocyte-complexes (COCs) retrieved: 5.5 (5.0-7.0) versus 6.0 (5.0-6.2), respectively, and fertilization rates: 57.7% (50.0-66.7) versus 50.0% (44.8-65.5), respectively. Live birth rates were similar between the groups (20.5% versus 16.7%, RD: + 3.8%, 95% CI: -8.5 to +16.1, respectively). Prolongation of time interval between HCG administration and oocyte retrieval from 36 h to 38 h does not affect oocyte retrieval rate.

Comparative Effectiveness of Therapeutic Interventions in Pregnancy and Lactation-Associated Osteoporosis: A Systematic Review and Meta-analysis.

CONTEXT: The optimal management of pregnancy and lactation-associated osteoporosis (PLO) has not been designated. OBJECTIVE: To systematically review the best available evidence regarding the effect of different therapeutic interventions on bone mineral density (BMD) and risk of fractures in these patients. METHODS: A comprehensive search was conducted in PubMed/Scopus databases until December 20, 2022. Data were expressed as weighted mean difference (WMD) with 95% CI. The I2 index was employed for heterogeneity. Studies conducted in women with PLO who received any antiosteoporosis therapy were included. Studies including women with secondary causes of osteoporosis or with transient osteoporosis of the hip were excluded. Data extraction was independently completed by 2 researchers. RESULTS: Sixty-six studies were included in the qualitative analysis (n = 451 [follow-up time range 6-264 months; age range 19-42 years]). The increase in lumbar spine (LS) BMD with calcium/vitamin D (CaD), bisphosphonates, and teriparatide was 2.0% to 7.5%, 5.0% to 41.5%, and 8.0% to 24.4% at 12 months, and 11.0% to 12.2%, 10.2% to 171.9%, and 24.1% to 32.9% at 24 months, respectively. Femoral neck (FN) BMD increased by 6.1% with CaD, and by 0.7% to 18% and 8.4% to 18.6% with bisphosphonates and teriparatide (18-24 months), respectively. Meta-analysis was performed for 2 interventional studies only. Teriparatide induced a greater increase in LS and FN BMD than CaD (WMD 11.5%, 95% CI 4.9-18.0%, I2 50.9%, and 5.4%, 95% CI 1.2-9.6%, I2 8.1%, respectively). CONCLUSION: Due to high heterogeneity and lack of robust comparative data, no safe conclusions can be made regarding the optimal therapeutic intervention in women with PLO.

Polycystic ovary syndrome and type 2 diabetes mellitus: A state-of-the-art review.

Polycystic ovary syndrome (PCOS) often coexists with a wide spectrum of dysglycemic conditions, ranging from impaired glucose tolerance to type 2 diabetes mellitus (T2D), which occur to a greater extent compared to healthy body mass index-matched women. This concurrence of disorders is mainly attributed to common pathogenetic pathways linking the two entities, such as insulin resistance. However, due to methodological flaws in the available studies and the multifaceted nature of the syndrome, there has been substantial controversy as to the exact association between T2D and PCOS which has not yet been elucidated. The aim of this review is to present the best available evidence regarding the epidemiology of dysglycemia in PCOS, the unique pathophysiological mechanisms underlying the progression of dysglycemia, the most appropriate methods for assessing glycemic status and the risk factors for T2D development in this population, as well as T2D risk after transition to menopause. Proposals for application of a holistic approach to enable optimal management of T2D risk in PCOS are also provided. Specifically, adoption of a healthy lifestyle with adherence to improved dietary patterns, such the Mediterranean diet, avoidance of consumption of endocrine-disrupting foods and beverages, regular exercise, and the effect of certain medications, such as metformin and glucagon-like peptide 1 receptor agonists, are discussed. Furthermore, the maintenance of a healthy weight is highlighted as a key factor in achievement of a significant reduction of T2D risk in women with PCOS.

Estrogen and bones after menopause: a reappraisal of data and future perspectives.

Menopausal hormone therapy (MHT) is effective in preventing menopause-related bone loss and decreasing vertebral, non-vertebral and hip fracture risk. MHT contains estrogens that exert both antiosteoclastic and osteoanabolic effects. These effects are dose-dependent, as even ultra-low doses preserve or increase bone mineral density. The transdermal route of administration is effective on cancellous and cortical bone, although fracture data are still lacking. Hormone replacement therapy is the treatment of choice to preserve skeletal health in women with premature ovarian insufficiency and early menopause. MHT can be considered in women aged < 60 years or within 10 years since menopause as, in this population, benefits outweigh possible risks, such as breast cancer and cardiovascular events. Despite the ensuing bone loss after MHT discontinuation, a residual antifracture effect persists. However, in women at risk of fracture, subsequent antiosteoporotic therapy may be needed, either with an antiosteoclastic or osteoanabolic agent. In any case, longitudinal data from randomized controlled trials comparing different estrogen doses and routes of administration, as well as designating the optimal treatment strategy after MHT discontinuation, are needed to elucidate these issues further.

Risk of type 2 diabetes mellitus in polycystic ovary syndrome is associated with obesity: a meta-analysis of observational studies.

PURPOSE: The exact risk of type 2 diabetes mellitus (T2DM) in women with polycystic ovary syndrome (PCOS) is unknown. It is also unclear if obesity independently increases T2DM risk in this population. The aim of this study was to systematically review and synthesize the best available evidence regarding the association between PCOS and T2DM, stratified according to obesity status. METHODS: A comprehensive search was conducted in PubMed, CENTRAL and Scopus databases up to October 31, 2020. Data are expressed as relative risk (RR) with 95% confidence interval (CI). The I2 index was employed for heterogeneity. RESULTS: The eligibility criteria were fulfilled by 23 studies (319,780 participants; 60,336 PCOS and 8847 type 2 diabetes cases). Women with PCOS demonstrated a higher risk of T2DM than those without PCOS (RR 3.45, 95% CI, 2.95-4.05, p < 0.001; I2 81.6%). This risk remained significant both in studies matched or unmatched for participants' age. With regard to body mass index (BMI), the RR for developing T2DM in obese and non-obese PCOS women compared with their non-PCOS counterparts was 3.24 (95% CI 2.25-4.65; p < 0.001; I2 30.9%) and 1.62 (95% CI 0.14-18.50; p = 0.70; I2 89.9%), respectively. The RR for developing T2DM was 3.85 (95% CI 1.99-7.43; p < 0.001; I2 46.2%) in obese compared with non-obese women with PCOS. This was also the case for overweight compared with lean women with PCOS. CONCLUSIONS: Women with PCOS present an increased risk of T2DM compared with non-PCOS women only if they are obese/overweight.

Decline in anti-Müllerian hormone concentrations following radioactive iodine treatment in women with differentiated thyroid cancer: A systematic review and meta-analysis.

AIM: Radioactive iodine (RAI) is frequently used as adjuvant therapy in patients with differentiated thyroid cancer (DTC). However, its effect on ovarian reserve has not been fully elucidated, with studies yielding inconsistent results. The aim of this study was to systematically review and meta-analyze the best available evidence regarding the effect of RAI on ovarian reserve in premenopausal women with DTC. METHODS: A comprehensive literature search was conducted in PubMed, Cochrane and Scopus, through to December 6th, 2020. Data were expressed as weighted mean difference (WMD) with a 95% confidence interval (CI). The I2 index was used to assess heterogeneity. RESULTS: Four prospective studies were included in the qualitative and quantitative analysis. Anti-Müllerian hormone (AMH) concentrations decreased at three (WMD -1.66 ng/ml, 95% CI -2.42 to -0.91, p<0.0001; I2 0%), six (WMD -1.58, 95% CI -2.63 to -0.52, p=0.003; I2 54.7%) and 12 months (WMD -1.62 ng/ml, 95% CI -2.02 to -1.22, p<0.0001; I2 15.5%) following a single RAI dose compared with baseline (three studies; n=104). With respect to follicle-stimulating hormone (FSH) concentrations, no difference was observed at six (WMD +3.29 IU/l, 95% CI -1.12 to 7.70, p=0.14; I2 96.8%) and 12 months (WMD +0.13 IU/l, 95% CI -1.06 to 1.32, p=0.83; I2 55.2%) post-RAI compared with baseline (two studies; n=83). No data were available for antral follicle count. CONCLUSIONS: AMH concentrations are decreased at three months and remain low at 6 and 12 months following RAI treatment in women with DTC. No difference in FSH concentrations post-RAI is observed.

The effect of statins on semen parameters in patients with hypercholesterolemia: A systematic review.

BACKGROUND: Statins constitute the mainstay of treatment in patients with hypercholesterolemia. However, their effect on semen parameters is unknown. OBJECTIVE: This study aimed to systematically review the best available evidence regarding the effect of statins on ejaculate volume and sperm concentration, motility, morphology, or vitality. MATERIALS/METHODS: A comprehensive search was conducted in PubMed, CENTRAL and Scopus databases up to January 10, 2021. Either randomized-controlled trials or prospective cohorts, conducted in males with hypercholesterolemia, were included. RESULTS: Four studies, published between 1992 and 2014, were eligible. The number of participants ranged from 8 to 120 (n = 161). Study duration ranged from 14 to 48 weeks. The type and dose of statin used were pravastatin 20-80 mg/day and simvastatin 20-40 mg/day. With regard to ejaculate volume (n = 3) and sperm concentration (n = 4), no effect was shown with either pravastatin or simvastatin. Regarding sperm motility, either an increase (n = 2; pravastatin, simvastatin), decrease (n = 1; pravastatin), or no effect (n = 1; pravastatin, simvastatin) was found. With respect to sperm morphology, either a decrease (n = 2; pravastatin, simvastatin) or no effect (n = 2; pravastatin, simvastatin) was shown. Concerning sperm vitality, a single study showed a decrease with simvastatin. Because of the high heterogeneity of the populations studied and the limited number of studies, a meta-analysis was not performed. CONCLUSION: This is the first systematic review on the effect of statins on semen parameters. As there is no evidence for such a detrimental effect, no specific approach has to be suggested regarding the preservation of reproductive function in men with hypercholesterolemia.

Female Infertility and Cardiovascular Risk - A Hype or an Underestimated Reality?

Infertility may be an early indicator of later-life health risk development, such as cardiovascular disease (CVD), the leading cause of death globally. Various infertility-associated factors such as female age, polycystic ovarian syndrome, endometriosis and metabolic syndrome are also risk factors for CVD. Whether there is a real association between female infertility and CVD, given that common pathways lead to both entities, or since both female infertility and CVD share a common basis, needs to be further investigated. If such an association is confirmed, infertile women might benefit from the initiation of preventive strategies aiming to control CVD risk factors. Thus, female infertility may represent an early indicator of future CVD and concomitantly a unique opportunity to identify women at increased risk for developing CVD. It is therefore imperative that large population- based studies are performed to elucidate this issue further and promote public awareness, if necessary.

Cardiovascular Complications in Patients with Turner's Syndrome.

Turner's or Turner syndrome (TS) is the most prevalent chromosomal abnormality in live female births. Patients with TS are predisposed to an increased risk of cardiovascular diseases (CVD), mainly due to the frequently observed congenital structural cardiovascular defects, such as valvular and aortic abnormalities (coarctation, dilatation, and dissection). The increased prevalence of cardiometabolic risk factors, such as arterial hypertension, insulin resistance, diabetes mellitus, dyslipidaemia, central obesity, and increased carotid intima-media thickness, also contribute to increased morbidity and mortality in TS patients. Menopausal hormone therapy (MHT) is the treatment of choice, combined with growth hormone (GH). Although MHT may, in general, ameliorate CVD risk factors, its effect on CVD mortality in TS has not yet been established. The exact effect of GH on these parameters has not been clarified. Specific considerations should be provided in TS cases during pregnancy, due to the higher risk of CVD complications, such as aortic dissection. Optimal cardiovascular monitoring, including physical examination, electrocardiogram, CVD risk factor assessment, and transthoracic echocardiography, is recommended. Moreover, the cardiac magnetic resonance from the age of 12 years is recommended due to the high risk of aortic aneurysm and other anatomical vascular complications.

Vitamin D supplementation and fracture risk: Evidence for a U-shaped effect.

During the last decade, a cascade of evidence has questioned the anti-fracture efficacy of vitamin D supplementation. In general, vitamin D status, reflected by serum 25-hydroxy-vitamin D [25(OH)D] concentrations, seems to predict fracture risk and bone mineral density (BMD). Despite the well-documented detrimental effect of vitamin D deficiency on bones, vitamin D monotherapy does not seem to reduce the risk of fractures. On the other hand, high vitamin D doses, either at monthly (60,000-100,000 IU) or daily intervals (>4000 IU), appear to be harmful with regard to falls, fracture risk and BMD, especially for people without vitamin D deficiency and at low fracture risk. Therefore, a U-shaped effect of vitamin D on the musculoskeletal system may be supported by the current evidence. Vitamin D supplementation could be of value, at daily doses of at least 800 IU, co-supplemented with calcium (1000-1200  mg/day), in elderly populations, especially those with severe vitamin D deficiency [25(OH)D <25-30  nmol/L (<10-12  ng/mL)], although its anti-fracture and anti-fall efficacy is modest. Good compliance and at least 3-5 years of therapy are required.

Polycystic ovary Syndrome in Adolescents: Pitfalls in Diagnosis and Management.

PURPOSE OF REVIEW: Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder during a woman's reproductive lifespan, with well-documented diagnostic criteria and therapeutic strategies in adults; the same is not necessarily true for adolescents. The purpose of this review was to identify frequent pitfalls in PCOS diagnosis and management during adolescence. RECENT FINDINGS: Although there is no global consensus on the definition, most experts converge to the presence of both oligo/amenorrhea and (clinical and/or biochemical) hyperandrogenism, as a prerequisite for diagnosis in adolescents. The former criterion includes: (a) consecutive menstrual intervals > 90 days even in the first year after menarche; (b) menstrual intervals persistently < 21 or > 45 days for ≥ 2 years after menarche; or (c) lack of menses by the age of 15 or 2-3 years after pubarche. However, these menstrual irregularity patterns may overlap with other common entities in adolescents, such as frequent or infrequent uterine bleeding or anovulation due to immaturity of the hypothalamic-pituitary-ovarian axis. Clinical signs of hyperandrogenism are obscure, without well-validated criteria. Finally, the criterion of polycystic morphology cannot be safely used in adolescents, mostly due to technical limitations of the transabdominal ultrasound. Except for the efficacy of lifestyle intervention in overweight and obese adolescents with PCOS, limited and low-quality data exist regarding the available medications, such as oral contraceptives, metformin, and anti-androgens. Individualized management, guided by clinical experience and research data and close monitoring appear the most effective approach in this PCOS population for optimal control of its reproductive and metabolic outcomes. Research focusing on PCOS genetic and molecular mechanisms may elucidate what diagnostic and therapeutic strategies will be most appropriate in adolescents with PCOS in the future.