Abstract
BACKGROUND
Ovarian endometrioma is a frequent manifestation of endometriosis in women of reproductive age. Several issues related to its space occupying effects, local reactions and surgical ...removal continue to be actively debated today. The impact of ovarian endometrioma per se on ovarian reserve is still controversial and the effect of ovarian surgery is still actively discussed. Furthermore, the optimal biomarker of ovarian reserve estimation in women with ovarian endometrioma is still under examination. Additionally, there is no consistent agreement on the effect of endometrioma bilaterality on ovarian reserve.
OBJECTIVE AND RATIONALE
The objective of this systematic review and meta-analysis was to study the impact of unilateral versus bilateral ovarian endometrioma on ovarian reserve biomarkers before and after endometrioma cystectomy.
SEARCH METHODS
We performed an extensive electronic database search employing PubMed, EBSCO, Web of Science, ClinicalTrials.gov and the Cochrane Library, to identify published research articles published between January 2000 and October 2018. Search terms included endometriotic cyst OR endometrioma OR endometriomata, cystectomy OR resection OR stripping OR removal OR excision and infertility OR subfertility. Only prospective controlled studies that compared the impact of unilateral versus bilateral ovarian endometriotic cystectomy on ovarian reserve tests in the same setting were included. Studies which included cases with PCOS, ovarian failure, early menopause, oral contraception treatment, or prior chemotherapy and/or radiotherapy or ovarian surgery, were excluded from evaluation. We used the Newcastle–Ottawa Scale for assessing the quality of studies found eligible for meta-analysis. We registered the systematic review on PROSPERO and its number is CRD42018117170.
OUTCOMES
Twelve studies were eligible for meta-analysis including collectively 783 women: 489 and 294 in the unilateral and bilateral groups, respectively. The included studies had a low risk of bias. The pre-operative weighted mean difference (WMD) showed that serum AMH levels did not differ significantly between the groups. Conversely, AMH levels were significantly (P < 0.05) lower in bilateral groups than in unilateral groups at the early, intermediate and late post-operative periods, corresponding WMDs of 0.78 ng/ml (95% CI: 0.41–1.15), 0.59 ng/ml (95% CI: 0.14–1.04) and 1.08 ng/ml (95% CI: 0.63 to 1.52), respectively. Heterogeneity among eligible studies reporting on before the operation and at the early and intermediate post-operative periods was high. Pre-operative and post-operative AFC values were not significantly different between the groups. The heterogeneity among the studies reporting on AFC was high. Analysis of each of the unilateral and bilateral groups separately showed a significant and sustained serum AMH drop by 39.5% and 57.0%, respectively from baseline to after the operation.
WIDER IMPLICATIONS
Our results challenge the concept that endometrioma per se adversely affects ovarian reserve, whereas endometrioma cystectomy, especially as bilateral operation, has a deleterious and sustained effect on ovarian reserve. AMH seems to be a more appropriate biomarker of ovarian reserve than AFC in cases with endometrioma. Since low AMH implies a shorter reproductive lifespan, excision of endometrioma should be cautiously considered, especially in bilateral cases.
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.
Endometriosis is a chronic, universal, and prevalent disease estimated to affect up to 1:10 women of reproductive age. Endometriosis-associated ovarian cancer (EAOC) developing at reproductive age is ...challenging and of concern for women and practitioners alike. This outlook review focuses on the occurrence of EAOC, especially in infertile women or those planning for a future pregnancy, from the perspective of a reproductive endocrinologist, based on recent evidence. Contemporary pathogenesis, genetic profiles, evidence of causality, clinical diagnosis, prognosis, and up-to-date management are discussed. EAOC seems to be merely associated with endometrioma and includes clear-cell and endometrioid ovarian carcinoma. Although endometrioma is frequently found in women of reproductive age (up to 1:18 of women), EAOC appears to be a rare occurrence. These women are of more advanced reproductive age, nulliparous, and hyperestrogenic, with a large-sized unilateral endometrioma (>9 cm) containing solid components and papillary projections. Each case suspected to have EAOC has specific characteristics, and a multidisciplinary discussion and appropriate patient counseling should be conducted to reach an optimal therapeutic plan. Since most of these cases are diagnosed at an early stage with a favorable prognosis, fertility-sparing surgery may be feasible. The pros and cons of fertility preservation techniques should be discussed.
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
were used to assess heterogeneity.
Of the 843 papers retrieved, 14 (
= 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.
Probiotic supplements may improve glycemic control and lipid profile and reduce neonatal birth weight in women with GDM.
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.
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.
Databases of PubMed, ClinicalTrials.gov, the Cochrane Library, Web of Science, and EBSCO were searched between January 2000 and October 2020.
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.
Two authors performed the screening and data extraction independently.
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.
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.
Abstract Large-scale studies show endometriosis linked to earlier menopause onset. Recent research targeting women with laparoscopically diagnosed endometriosis found an increase in cases of early ...natural menopause. Furthermore, recent large-scale cohort studies have found a correlation between endometriosis and an increased risk of cardiovascular disease (CVD). Understanding the causality of early menopause, particularly natural menopause, and cardiovascular risks in women with endometriosis could help medical professionals develop effective strategies for early prevention and new therapies. Endometriosis, early menopause, and cardiovascular risks may be linked by primary or secondary mechanisms. Primary mechanisms involve shared pathways that can lead to all morbidities, while secondary occur due to delayed consequences of management strategies. In these large-scale cohort studies, relevant risk and confounding factors, such as oophorectomy, were considered to refine estimates of associations. However, none of the studies considered endometriotic cystectomy, a globally accepted treatment for endometriosis-associated pelvic pain and infertility, as a mediating factor. There is substantial evidence to indicate that endometriotic cystectomy harms ovarian reserve and may lead to early menopause in cases of multiple surgeries or bilateral cases. Early menopause is a well-established risk factor for CVD. To thoroughly examine the link between endometriosis and early menopause, particularly natural menopause, and their connection with cardiovascular risks, it is imperative to consider all the possible factors that may affect the results, such as endometriotic cystectomy. This will enable us to obtain the most accurate and adjusted hazard ratio.
COVID-19 is a complex disease with a multifaceted set of disturbances involving several mechanisms of health and disease in the human body. Sex hormones, estrogen, and testosterone, seem to play a ...major role in its pathogenesis, development, spread, severity, and mortalities. Examination of factors such as age, gender, ethnic background, genetic prevalence, and existing co-morbidities, may disclose the mechanisms underlying SARS-CoV-2 infection, morbidity, and mortality, paving the way for COVID-19 amelioration and substantial flattening of the infection curve. In this mini-review, we focus on the role of testosterone through a discussion of the intricate mechanisms of disease development and deterioration. Accumulated evidence suggests that there are links between high level (normal male level) as well as low level (age-related hypogonadism) testosterone in disease progression and expansion, supporting its role as a double-edged sword. Unresolved questions point to the essential need for further targeted studies to substantiate these contrasting mechanisms.
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