Testicular fine-needle aspiration in infertile men with absolute non-obstructive azoospermia: A single-centre cohort study.

BACKGROUND: The methodology of surgically extracted sperm cells in fertility treatments remains debated, mainly due to the lack of data evaluating its predictive value on treatment outcomes. AIM: To gain insight into the effectiveness of testicular fine-needle aspiration (TEFNA) in a cohort of infertile men with absolute non-obstructive azoospermia and to examine whether the number of retrieved sperm cells affects the fertilisation rate. MATERIALS AND METHODS: A total of 89 infertile men, aged 26-47, meticulously diagnosed with non-obstructive azoospermia, participated in the study. All participants underwent TEFNA. The primary outcome measure was the TEFNA success rate in retrieving mature sperm. The secondary outcome measures included fertilisation rate, clinical pregnancy rates, and live births associated with the retrieved sperm. RESULTS: Sperm cells were successfully retrieved from 40 out of 89 patients (45%) with no significant postoperative complications. Retrieval of up to ten sperm cells occurred in 11 procedures (25%); ten procedures (22.7%) resulted in producing dozens of sperm cells, and 100s to 1000s of sperm cells were obtained from the remainder of 23 procedures (52.3%). Patients whose TEFNA resulted in only a few sperm cells had a much lower fertilisation rate (16.6%) than the other two groups (40.1% and 47.2%, respectively, P = 0.003). CONCLUSIONS: The utilisation of TEFNA for sperm extraction in men with non-obstructive azoospermia is a simple, fast-learning, effective, and safe treatment option. In cases where sperm retrieval was successful, the fertilisation rate was strongly related to the number of sperm cells obtained.

Endometrioma surgery-a systematic review and meta-analysis of the effect on antral follicle count and anti-Müllerian hormone.

OBJECTIVE: Accurate preoperative counseling about whether an endometriotic cystectomy has a detrimental effect on the ovarian reserve has been a considerable challenge, because studies assessing the postoperative antral follicle counts and anti-Müllerian hormone levels have reported conflicting results. Our objective was to explore the impact of endometriotic cystectomy on both the anti-Müllerian hormone levels and antral follicle counts, with focus on prospective studies in which both variables were measured for each woman concurrently (overcoming unmeasured confounding), in the same setting (overcoming surgical technique differences), and at the same 3 postoperative time points, namely early (1-6 weeks), intermediate (2-6 months) and late (9-18 months), to overcome time-sensitive changes. DATA SOURCES: Databases of PubMed, ClinicalTrials.gov, the Cochrane Library, Web of Science, and EBSCO were searched between January 2000 and October 2020. STUDY ELIGIBILITY CRITERIA: Only prospective cohort studies that evaluated the impact of endometriotic stripping cystectomy on anti-Müllerian hormone levels and antral follicle counts in the same women, at matching time points, and in the same setting were eligible. STUDY APPRAISAL AND SYNTHESIS METHODS: Two authors performed the screening and data extraction independently. RESULTS: A total of 14 prospectively designed studies were eligible for the meta-analysis and included 650 women. The included studies had a low risk of bias. The postoperative weighted mean differences in serum anti-Müllerian hormone levels dropped significantly when compared with the preoperative levels by an estimated 1.77 ng/mL (95% confidence interval, 0.77-2.77; P<.001), 1.17 ng/mL (95% confidence interval, 0.66-1.67; P<.001), and 2.13 ng/mL (95% confidence interval, 1.61-2.65; P<.001) at the early (1-6 weeks), intermediate (2-6 months), and late (9-18 months) time points, respectively. This corresponded to a mean reduction in serum anti-Müllerian hormone levels at each of the 3-time points of 44.4%, 35.1%, and 54.2%, respectively. Conversely, the postoperative weighted mean difference in the antral follicle count estimates did not change significantly at any of the 3 time points; the early antral follicle count was 0.70 (95% confidence interval, -2.71 to 3.56; P=.63), the intermediate count was -0.94 (95% confidence interval, -2.53 to 0.65; P=.25), and the late count was 2.58 (95% confidence interval, -0.43 to 5.58; P=.09). Overall, high levels of heterogeneity were encountered (I2 ranging between 92% and 94% for the anti-Müllerian hormone levels and between 94% and 98% for the antral follicle counts at the 3 time points), which were attenuated when similar anti-Müllerian hormone assays were compared, and the meta-regression suggested that age did not contribute to heterogeneity. CONCLUSION: Endometriotic cystectomies are associated with a significant reduction in the serum anti-Müllerian hormone levels but not in the antral follicle counts, with the detrimental effects on the anti-Müllerian hormone levels consistently detectable at the early-, intermediate-, and late-postoperative time points. In women with endometrioma, the anti-Müllerian hormone level may provide a more accurate assessment of the risk for iatrogenic depletion of the ovarian reserve.

Does large endometrioma per se increase AMH level?

Women with endometriosis, especially those with endometrioma, present a considerable challenge for ovarian reserve appraisal. This diagnostic difficulty arises from several fundamental questions inherently linked to patient management: the potential influence of endometrioma on ovarian reserve; the adverse effect of ovarian surgery on ovarian reserve; and the adequacy of the established ovarian reserve biomarkers, anti-Müllerian hormone and antral follicle count, to appraise ovarian reserve accurately in these women. Until recently, a key argument was that the development and growth of endometriomas is associated with a progressive damage to normal ovarian tissue, resulting in a concomitant reduction in serum AMH levels. Contrary to this widely accepted position; recent studies have reported that, in women with no previous history of ovarian surgery, AMH levels were increased in women with large endometriomas. These findings are surprising and, if replicated, would have substantial clinical implications. In this commentary, we would, however, urge caution before these reports lead to systematic changes in clinical practice, and recommend urgent replication as the finding linking large endometrioma to high serum AMH levels seems to be biologically implausible, and contradicts the existing extensive body of research.

Protein C global assay evaluation in naturally conceived vs. assisted reproduction-achieved twin pregnancies: a prospective longitudinal study.

PURPOSE: Protein C global assay tests the global function of the protein C pathway, the most clinically significant anticoagulant pathway in humans. The objective of this study is to assess the difference in protein C global assay levels, throughout twin gestation, in naturally conceiving and ART-treated women. METHODS: This is a prospective cohort longitudinal study of pregnant women with twin gestation. Protein C Global evaluation was performed on frozen blood samples. Ninety-eight women with twin pregnancy, thirty-eight naturally conceived and sixty following ART, were evaluated on four occasions: during the first, second, and third trimesters, and 6 weeks or later after delivery (baseline). RESULTS: Protein C global assay levels were lower throughout pregnancy as compared to basal levels in both the naturally conceived and ART-conceived groups. However, protein C global assay levels were similar between the ART-conceived and naturally conceived twin pregnancies in all three trimesters. Perinatal complications were associated with decreased protein C global assay levels during the third trimester, although no difference was encountered between naturally conceived and ART-complicated twin pregnancies. CONCLUSION: While protein C global assay levels drop during twin pregnancy, there is no difference between ART-conceived and naturally conceived gestations. Decreased levels of protein C global assay during the third trimester were similarly associated with perinatal complications in both groups. Our results imply that twin pregnancy of itself is a more dominant factor for perinatal complications as compared to other factors, such as subfertility or the exposure to ART per se.

Is there an impact of the COVID-19 pandemic on male fertility? The ACE2 connection.

The viral pandemic of the coronavirus disease 2019 (COVID-19), generated by a novel mutated severe acute respiratory syndrome coronavirus (SARS-CoV-2), has become a serious worldwide public health emergency, evolving exponentially. While the main organ targeted in this disease is the lungs, other vital organs, such as the heart and kidney, may be implicated. The main host receptor of the SARS-CoV-2 is angiotensin converting enzyme 2 (ACE2), a major component of the renin-angiotensin-aldosterone system (RAAS). The ACE2 is also involved in testicular male regulation of steroidogenesis and spermatogenesis. As the SARS-CoV-2 may have the potential to infect the testis via ACE2 and adversely affect male reproductive system, it is essential to commence with targeted studies to learn from the current pandemic, with the possibility of preemptive intervention, depending on the findings and time course of the continuing pandemic.

An exome-wide exploration of cases of primary ovarian insufficiency uncovers novel sequence variants and candidate genes.

Primary ovarian insufficiency (POI) implies the cessation of menstruation for several months in women before the age of 40 years and is a major cause of infertility. The study of the contribution of genetic factors to POI has been fueled by the use of whole exome sequencing (WES). Here, to uncover novel causative pathogenic variants and risk alleles, WES has been performed in 12 patients with familial POI (eight unrelated index cases and two pairs of sisters) and six women with early menopause and family history of POI (four index cases and one pair of sisters). Likely causative variants in NR5A1 and MCM9 genes were identified as well as a variant in INHA that requires further investigation. Moreover, we have identified more than one candidate variant in 3 out of 15 familial cases. Taken together, our results highlight the genetic heterogeneity of POI and early menopause and support the hypothesis of an oligogenic inheritance of such conditions, in addition to monogenic inheritance.

Is there a difference in ovarian reserve biomarkers and ovarian response between the right and left ovaries?

RESEARCH QUESTION: Is there a difference in ovarian reserve biomarkers and ovarian response between the right and left ovaries of infertile women undergoing IVF treatments? DESIGN: A total of 100 infertile women aged 27 to 37 years, diagnosed with either unexplained male factor or mechanical factor infertility, participated in the study. All women had both ovaries intact, and regular menstrual cycles with no previous diagnosis of polycystic ovaries or endometriosis. The data were collected separately for each ovary, and included parameters of basal sonographic ovarian reserve, as well as ovarian response to ovarian stimulation. RESULTS: Basal sonographic ovarian reserve markers were similar between the two ovaries. The right and left ovaries did not differ in their basal antral follicle count (AFC) (6.9 ± 3.9 versus 6.8 ± 3.8, respectively, P = 0.672), nor did they differ in their ovarian volume (10.3 ± 6.7 versus 9.8 ± 8.0 cm3, respectively, P = 0.636). Nevertheless, a superior right-sided ovarian response to ovarian stimulation was observed, with a significantly higher total number of follicles in the right compared with the left ovary (7.8 ± 4.3 versus 6.8 ± 4.2 follicles, respectively, P = 0.006), and a higher number of follicles ≥14 mm on the day of human chorionic gonadotrophin administration (4.9 ± 3.2 versus 3.8 ± 2.4 follicles, respectively, P = 0.002). CONCLUSIONS: Despite comparable basal AFC and ovarian volume, the two ovaries are distinguishable in their response to ovarian stimulation with a clear right-side preference. These findings imply that the superiority of right ovarian response may be derived from local pelvic factors, presumably a more efficient vascularization.

Does the empty follicle syndrome occur in cases of low number of maturing follicles in assisted reproduction?

The pathophysiology of the genuine empty follicle syndrome (EFS) is still debated. Ovarian aging has been contested as a cause of this condition. Our aim was to investigate the occurrence of the genuine EFS in cases of a low number of mature follicles in a prospective manner. Ninety-five infertile women were recruited and evaluated following conventional controlled ovarian stimulation (COS) with ≤ six follicles of ≥14 mm diameter on the day of hCG administration. Enrolled women were 37.5 ± 5.2 years of age with basal FSH level of 9.1 ± 3.7 mIU/L, antral follicle count (AFC) of 6.9 ± 4.6, and number of ≥14 mm follicles (on the day of hCG) of 3.4 ± 1.5. Among the 95 women, four were complicated by the genuine EFS (4.2%) with features of the depleted ovarian reserve. Comparison between these four cases and the 91 controls revealed significant differences between age, AFC, number of ≥14 mm follicles, and serum E2 level corresponding to 41.8 ± 1.7 versus 37.4 ± 5.2 years, 1.7 ± 0.6 versus 7.1 ± 4.5, 2.0 ± 0.8 versus 3.4 ± 1.5 follicles, and 356 ± 200 versus 975 ± 557 pg/mL, respectively. Post hoc analysis revealed that 56 among the 95 women fulfilled the Bologna criteria for poor ovarian response and all four cases matched the definition of the genuine EFS raising its incidence to 7.1% in this group. A logistic regression analysis showed that AFC was a significant factor in the development of the genuine EFS. We conclude that the genuine EFS complicates infertile women characterized by a low number of mature follicles. Our findings suggest that the mechanism behind this occurrence is associated with a more exhausted ovarian reserve.

Do young women with unexplained infertility show manifestations of decreased ovarian reserve?

PURPOSE: To investigate whether unexplained infertility at a young age demonstrates manifestations of decreased ovarian reserve. METHODS: A total of 100 women were divided into two equally sized groups. The study group comprised women aged ≤ 37 years diagnosed with unexplained infertility, and the control group included age-matched women with either mechanical factor or severe male factor infertility. RESULTS: Both groups were comparable in their basic characteristics. Overall, women with unexplained infertility presented with inferior ovarian reserve results set against women of the control group. The number of ≥ 14-mm follicles on the day of hCG administration was significantly lower in the study compared with the control group (7.0 ± 4.5 vs. 10.4 ± 4.1 follicles, respectively, P < 0.001). Likewise, basal serum FSH was higher in the study compared with the control group (8.4 ± 5.5 vs. 6.4 ± 1.7 IU/L, respectively, P = 0.015), while antral follicle count was lower (10.9 ± 6.6 vs. 16.2 ± 6.6 follicles, respectively, P < 0.001). Furthermore, women with unexplained infertility required a higher total dose of FSH for ovarian stimulation (2,923 ± 1,701 vs. 2,196 ± 941 IU/L, respectively, P = 0.010), but exhibited a lower number of retrieved oocytes (9.3 ± 6.3 vs. 15.6 ± 7.9 oocytes, respectively, P < 0.001), alongside a lower number of achieved embryos (5.3 ± 4.0 vs. 8.0 ± 4.7 embryos, respectively, P = 0.002). Interestingly, the cumulative clinical pregnancy rate was not significantly different between the two groups (44% vs. 58%, respectively, P = 0.163). CONCLUSIONS: Young women ≤ 37 years of age with unexplained infertility have clear manifestations of sub-optimal ovarian reserve set against controls. Our findings suggest that unexplained infertility at a young age may be a risk factor for developing poor ovarian response, specifically as a quantitative, rather than a qualitative, risk factor.

Identification of Premeiotic, Meiotic, and Postmeiotic Cells in Testicular Biopsies Without Sperm from Sertoli Cell-Only Syndrome Patients.

Sertoli cell-only syndrome (SCOS) affects about 26.3⁻57.8% of azoospermic men, with their seminiferous tubules containing only Sertoli cells. Recently, it was reported that testicular biopsies from nonobstructive azoospermic (NOA) patients contained germ cells, and that sperm could be found in the tubules of 20% of SCOS patients using testicular sperm extraction technology. Since the patients without sperm in their testicular biopsies do not have therapy to help them to father a biological child, in vitro maturation of spermatogonial stem cells (SSCs) isolated from their testis is a new approach for possible future infertility treatment. Recently, the induction of human and mice SSCs proliferation and differentiation was demonstrated using different culture systems. Our group reported the induction of spermatogonial cell proliferation and differentiation to meiotic and postmeiotic stages in mice, rhesus monkeys, and prepubertal boys with cancer using 3D agar and methylcellulose (MCS) culture systems. The aim of the study was to identify the type of spermatogenic cells present in biopsies without sperm from SCOS patients, and to examine the possibility of inducing spermatogenesis from isolated spermatogonial cells of these biopsies in vitro using 3D MCS. We used nine biopsies without sperm from SCOS patients, and the presence of spermatogenic markers was evaluated by PCR and specific immunofluorescence staining analyses. Isolated testicular cells were cultured in MCS in the presence of StemPro enriched media with different growth factors and the development of colonies/clusters was examined microscopically. We examined the presence of cells from the different stages of spermatogenesis before and after culture in MCS for 3⁻7 weeks. Our results indicated that these biopsies showed the presence of premeiotic markers (two to seven markers/biopsy), meiotic markers (of nine biopsies, cAMP responsive element modulator-1 (CREM-1) was detected in five, lactate dehydrogenase (LDH) in five, and BOULE in three) and postmeiotic markers (protamine was detected in six biopsies and acrosin in three). In addition, we were able to induce the development of meiotic and/or postmeiotic stages from spermatogonial cells isolated from three biopsies. Thus, our study shows for the first time the presence of meiotic and/or postmeiotic cells in biopsies without the sperm of SCOS patients. Isolated cells from some of these biopsies could be induced to meiotic and/or postmeiotic stages under in vitro culture conditions.

The effect of LH supplementation to the GnRH antagonist protocol in advanced reproductive ageing women: a prospective randomized controlled study.

OBJECTIVE: Although the fundamental significance of both LH and FSH for adequate ovarian folliculogenesis and steroidogenesis has been extensively discussed, the clinical implication of recombinant (r) LH to rFSH for ovarian stimulation employing the GnRH antagonist protocol remains to be elucidated. The aim of this prospective randomized controlled study was to explore whether rLH supplementation to rFSH following GnRH antagonist has an added value to the late follicular ovarian steroidogenesis in the advanced reproductive aged women. DESIGN AND SUBJECTS: Sixty-three consecutive infertile women above 35 years of age and/or with a previous low ovarian response admitted for IVF/ICSI treatment were prospectively randomized. Women in the study and control groups were similarly treated employing the rFSH 300 IU/day and the flexible GnRH antagonist 0·25 mg/day protocol. On the day of antagonist initiation, rLH 150 IU/day was added only to the study group and continued till the hCG day. RESULTS: Serum E2 level on hCG day did not significantly differ between the study and control groups, corresponding to 1268 ± 1006 and 1113 ± 669 pg/mL, respectively (P = 0·9). In the study group, the duration of GnRH antagonist administration was significantly lower than the control group corresponding to 5·0 ± 1·5 to 4·0 ± 1·5 days, respectively (P < 0·05). The total dosage of rFSH administration did not differ between the two groups. CONCLUSIONS: rLH supplementation to rFSH following GnRH antagonist administration employing the flexible protocol does not seem to significantly augment serum E2 level on the day of hCG administration in the advanced reproductive ageing women. This suggests that endogenous serum LH levels following GnRH antagonist initiation are sufficient for adequate late follicular ovarian steroidogenesis in this setting.

The association between multinucleated blastomeres and poor ovarian response under the Bologna criteria.

PURPOSE: To investigate the occurrence of multinucleated blastomeres (MNB) in poor ovarian response (POR) women defined under the Bologna criteria. METHODS: This observational study was designed in a prospective controlled manner. Among 380 cases evaluated for eligibility, 102 women were found suitable and recruited; 51 with POR in accordance with the Bologna criteria defined as the study group and 51 with normal ovarian response defined as the control group. RESULTS: Among the 51 women in each group, 8 and 2 did not achieve embryos in the study and control group, respectively (P < 0.05). The percentage of women that had at least one embryo with one MNB was significantly higher in the study as compared to the control group, corresponding to 49 and 29 %, respectively. The total number of embryos evaluated was 416; 167 in the study and 249 in the control groups. Among these embryos, the MNB rate was significantly higher in the study as compared to the control group, corresponding to 19 and 8 %, respectively. CONCLUSIONS: Blastomere multinuclearity is significantly more common in women and embryos of POR cases, defined under the Bologna criteria. Future studies are warranted to substantiate our observation that has the potential to be clinically implemented in this sub-group of women undergoing assisted reproductive technologies (ART) treatment.

Basic research in PCOS: are we reaching new frontiers?

Polycystic ovarian syndrome (PCOS) is the leading cause for anovulatory infertility. It is diagnosed by two of the following three clinical criteria: oligomenorrhoea, hyperandrogenism and polycystic appearance of the ovaries. Weight loss and physical activity can lead to ovulation and conception. Lowering of serum insulin normalizes androgen concentrations whereas ovulation induction often causes ovarian hyperstimulation. Theca cells from PCOS ovaries may be more responsive to insulin than cells from non-PCOS ovaries. Herein we review the research efforts at the genomic and cell function levels, as well as animal models, which have been made to elucidate the underlying mechanism that leads to PCOS. It appears that, despite the impressive amount of data that have been generated in these studies, the mechanism of this syndrome is still only partially understood. Polycystic ovarian syndrome (PCOS) is the leading cause for infertility, which is caused by anovulation. It is diagnosed by two of the following three clinical criteria: irregular and prolonged menstrual cycles, overt symptoms of excess androgens, which is revealed by acne and excess hair, and ultrasonographic appearance of the ovaries with multiple small follicles spread mainly near the ovarian surface, which gave it its name. Intentional weight loss and physical activity can lead to resumption of ovulation and not infrequently to conception as well. It was shown that lowering of serum insulin accounts for normalization of serum androgen levels, whereas ovulation induction with FSH often causes ovarian hyperstimulation. It is suggested that theca cells from PCOS ovaries may be more responsive to insulin than cells from non-PCOS ovaries. In this article we review the efforts to define the genes responsible for the syndrome and the studies at the cell function level, as well as animal models, which have been done to elucidate the underlying mechanism that leads to PCOS. Overall, it appears that despite the impressive amount of data that have been generated in these studies, the mechanism of this syndrome is still only partially understood.

Reduced protein C Global assay level in infertile women prior to IVF-ET treatment.

PURPOSE: In the last few years more robust evidence is emerging to point out at an increased rate of prematurity and low birth weight in singleton pregnancies following ART. Whether this increased rate is related to ART practice or to infertility per se, is still an open question. Our aim in this study was to explore this question by evaluating Protein C (ProC) Global assay in infertile women before ART treatment. METHODS: A cohort of 95 unselected and consecutive infertile women, eligible for ART, was prospectively recruited for the study. The control group included 77 matched healthy fertile women with a history of spontaneous conceptions. Pro C Global assay was evaluated in both groups. A full thrombophilic work-up was performed in the study group. RESULTS: ProC Global assay level was found to be significantly lower in the study as compared to the control group, corresponding to 0.78 ± 0.16 and 0.88 ± 0.16, respectively (P < 0.01). As well, abnormal ProC Global assay level of ≤ 0.8 was significantly higher in the study as compared to control group corresponding to 53 % and 29 %, respectively. ProC Global assay level was significantly lower in women within the study group found to have APCR, factor V Leiden and high factor VIII level, any thrombophilia or combined thrombophilia when compared to women without these thrombophilic risk factors. CONCLUSIONS: Reduced ProC Global assay level is encountered in infertile women prior to ART treatment. This finding may suggest a unique anticoagulation Protein C pathway in infertile as compared to fertile women. Further studies are encouraged to explore this finding.

The impact of ovarian endometrioma and endometriotic cystectomy on anti-Müllerian hormone, and antral follicle count: a contemporary critical appraisal of systematic reviews.

Currently, three crucial questions regarding the reliability of ovarian reserve measures in women with ovarian endometrioma during the reproductive age are being discussed. Firstly, the effects of endometriotic cystectomy on short and long-term ovarian reserve. Secondly, the accuracy of serum anti-Müllerian hormone (AMH) and antral follicle count (AFC) in estimating ovarian reserve in these cases. Thirdly, the impact of endometrioma itself on the ovarian reserve over time in such cases. The purpose of the present review is to critically assess available systematic reviews and meta-analyses that have explored these questions. Nine eligible reviews were found following a systematic search on PubMed.com and similarly assessed. These reviews varied considerably regarding the level of evidence, as per an identical comprehensive scoring system. Moderate to high-quality evidence demonstrates that endometriotic cystectomy, by the stripping technique, adversely affects ovarian reserve in the short and long term, up to 9-18 months post-surgery. Damage to ovarian reserve was considerable but more pronounced in bilateral cases than unilateral cases, equivalent to 39.5% and 57.0%, respectively. Repeat endometriotic cystectomy is detrimental to ovarian reserve. The impact of endometrioma diameter on ovarian reserve before or after surgery is still unclear. Moderate to high-quality evidence, relying on simultaneous assessment of both ovarian reserve measures, shows that AMH is sensitive while AFC is not in cases undergoing ovarian cystectomy. AMH should be the biomarker of choice for counseling and managing women with endometrioma in their reproductive age, especially before surgery. While there is some evidence to show that endometrioma per se may harm ovarian reserve, this evidence is not robust, and there is good-quality evidence to challenge this notion. It is necessary to conduct further targeted RCTs, systematic reviews, and meta-analyses based on solid methodological grounds to increase the level of evidence, refine quantitative estimates, investigate open questions, and decrease heterogeneity.

Low ovarian responders produce more progesterone per follicle than normal and high responders.

OBJECTIVE: Late follicular premature progesterone rise is a complex phenomenon encountered during assisted reproductive technology (ART) treatments; different etiologies can occur in the same patient. Low ovarian responders may be the best example, since higher FSH doses and ovarian aging-related changes may interact and generate a premature progesterone rise. This study aims to explore the correlation between progesterone levels on hCG day and the progesterone-to-follicle index and compare the progesterone-to-follicle index according to ovarian response. METHODS: We performed a retrospective, observational, analytic, cross-sectional, and cohort study at the Reproductive Endocrinology Department at Centro Médico Nacional 20 de November between January 2015 to January 2020. After verifying for normalcy, a Spearman Rho, Principal Component Analysis, and a simple linear regression model were performed. Treatment cycles were classified according to their ovarian response. Low-ovarian responders were classified according to the Bologna Criteria. Then an ANOVA test was performed to compare each group. RESULTS: Our results show that the progesterone-to-follicle index correlates best with progesterone levels on hCG day. Comparing all the ovarian responses, low ovarian responders have the highest progesterone-to-follicle index of the four groups. CONCLUSIONS: Low ovarian responders produce more progesterone per follicle than regular and high responders.

Effects of Probiotics on Glycemic Control and Metabolic Parameters in Gestational Diabetes Mellitus: Systematic Review and Meta-Analysis.

OBJECTIVES: To assess the effects of probiotic supplements on glycemic control and metabolic parameters in women with gestational diabetes mellitus (GDM) by performing a systematic review and meta-analysis of randomized controlled trials. The primary outcome was glycemic control, i.e., serum glucose and insulin levels. Secondary outcomes were maternal weight gain, neonatal birth weight, and lipid parameters. Weighted mean difference (WMD) was used. Cochrane's Q test of heterogeneity and I2 were used to assess heterogeneity. RESULTS: Of the 843 papers retrieved, 14 (n = 854 women) met the inclusion criteria and were analyzed. When compared with placebo, women receiving probiotic supplements had significantly lower mean fasting serum glucose, fasting serum insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglycerides, total cholesterol, and VLDL levels. Decreased neonatal birth weight was witnessed in supplements containing Lactobacillus acidophilus. CONCLUSION: Probiotic supplements may improve glycemic control and lipid profile and reduce neonatal birth weight in women with GDM.

Should pregnant women be screened for SARS-CoV-2 infection? A prospective multicenter cohort study.

OBJECTIVE: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ranges from asymptomatic to severe infection. We aimed to compare the prevalence of COVID-19 in asymptomatic pregnant versus nonpregnant women in order to establish recommendations for a COVID-19 screening strategy. METHODS: A prospective multicenter cohort study was conducted. Asymptomatic pregnant or nonpregnant women after March 2020 (the time when COVID-19 was first detected in north Israel) were tested for SARS-CoV-2 using nasopharyngeal reverse transcription polymerase chain reaction test, anti-nucleocapsid IgG, and anti-spike IgG. Diagnosis was made if at least one test result was positive. Pregnant women were tested between 34 and 42 weeks, mostly at birth. RESULTS: Among the 297 participating women, 152 were pregnant and 145 were nonpregnant. The prevalence of asymptomatic COVID-19 was similar between the groups (4 [2.6%] and 8 [5.5%], respectively; P = 0.2). All women with COVID-19 delivered healthy appropriate-for-gestational-age babies without malformations, at term. CONCLUSIONS: The rate of asymptomatic COVID-19 in pregnant women is low and comparable to the rate among nonpregnant women. Pregnancy outcomes are favorable. Future screening programs should consider that one of 25 screened asymptomatic women will be positive.