Vitamin D and reproductive disorders: a comprehensive review with a focus on endometriosis.

Vitamin D is a fat-soluble steroid hormone that was initially known only for regulating calcium and phosphorus levels and maintaining bone health. However, it was later discovered that many organs express vitamin D metabolizing enzymes and have a ligand for vitamin D, which regulates the expression of an extensive assortment of genes. As a result, vitamin D is indispensable for the proper function of organs, and its deficiency is believed to be a critical factor in symptoms and disorders such as cardiovascular diseases, autoimmune diseases, and cancers. The significance of vitamin D in reproductive tissues was recognized later, and studies have revealed its crucial role in male and female fertility, as well as proper reproductive function during pregnancy. Vitamin D deficiency has been identified as a risk factor for infertility, gonadal cancers, pregnancy complications, polycystic ovary syndrome, and endometriosis. However, data investigating the association between vitamin D levels and reproductive disorders, including endometriosis, have encountered inconsistencies. Therefore, the present study aims to review existing research on the effect of vitamin D on proper reproductive function, and the role of deficiency in reproductive diseases and specifically focuses on endometriosis.

Mendelian randomization reveals the impact of diet on infertility in men and women.

Background: Although studies on the effects of diet on fertility has progressed, some cumulative evidence has piled against popular hypotheses. The aim of our study was to investigate the effects of 31 diets including 23 individual dietary intakes and 8 dietary habits on infertility in men and women. Methods: The datas of diets and infertility were collected from genome-wide association studies (GWAS). Mendelian randomization (MR) methods were used to analyze causal relationships. Multivariate MR (MVMR) adjusted for the effects of other exposures on causality. And MR-Egger, Cochran's Q, radial MR, and MR-PRESSO tests were employed to assess heterogeneity and horizontal pleiotropy. Results: Our study found that coffee intake (OR, 3.6967; 95% CI, 1.0348 - 13.2065; P = 0.0442) and cooked vegetable intakes (OR, 54.7865; 95% CI, 2.9011 - 1030.5500; P = 0.0076) increased the risk of male infertility. For women, beer was a risk factor for infertility (OR, 4.0932; 95% CI, 1.8728 - 8.9461; P = 0.0004); but processed meat was negatively associated with infertility (OR, 0.5148; 95% CI, 0.2730 - 0.9705; P = 0.0401). MVMR demonstrated selenium as a protective factor against female infertility (OR, 7.4474e-12; 95% CI, 5.4780e-22 - 1.0125e-01; P = 0.0314). Conclusion: We found the causal relationships between four diets and infertility. We look forward to more high-quality epidemiologic studies to prove our conclusions.

Establishment of an Experimental Mouse Model of Endometrioma to Study its Related Infertility.

Endometrioma (OMA), a subtype of endometriosis characterized by the formation of endometriotic cysts in the ovaries, affects 17-44% of individuals diagnosed with endometriosis. Women with OMA often experience compromised fertility, yet the exact mechanisms underlying OMA-associated infertility remain unclear. Notably, existing animal models simulate superficial peritoneal endometriosis (SUP) and deep infiltrating endometriosis (DIE), leaving a notable gap in research focused on OMA. In response to the gap of knowledge, this paper introduces a pioneering OMA-simulating mouse model and provides a comprehensive description of the techniques and procedures employed in the model. With a high success rate of 83% and ovarian lesion specificity, this model holds significant promise for advancing our understanding of OMA, particularly in the context of infertility. It offers a valuable platform for conducting targeted research into OMA-associated fertility challenges, potentially paving the way for improved diagnostic and therapeutic strategies in the field of reproductive medicine.

"TB - Mindedness"-the only way to beat "the great mimicker": A case series with atypical presentation of female genital tuberculosis.

BACKGROUND: Incidence of Tuberculosis (TB) cases in India reported in 2019 is 193 per 1 lakh population [National Tuberculosis Elimination Plan (NTEP)]. In India, annual extra pulmonary TB burden is 20-25%, of which 4% of cases are of urogenital origin (Revised National TB Control Programme, 2019; World Health Organization, 2019). The Ministry of Health and Family Welfare has made a target of eliminating tuberculosis by 2025 under the NTEP by the process of identification, notification and treatment of cases. Tuberculosis being a leading cause of infertility in developing countries, employing best clinical practices and being "TB-minded" will also save the patient of enormous anxiety and uncertainity and also decrease the time gap between clinical presentation and diagnosis to optimize fertility outcome. METHODOLOGY: A prospective cohort study of cases presenting with unusual findings and ultimately being diagnosed as genital tuberculosis was conducted in the gynaecology OPD, AIIMS, New Delhi, from November 2020 to November 2021 (1 year). Patients were investigated judiciously, diagnosis made and followed up for their response to anti tuberculosis therapy (ATT). RESULTS: This data comprises of conglomerate of ten cases with unconventional exhibition of genital tuberculosis. 70% of the cases presented with pain lower abdomen not specifically related to menstrual cycle and often confused with IBD. Tubo ovarian mass (70%) mimicking as simple ovarian cyst, ovarian carcinoma or endometriosis was the most common clinical finding we came across.

Comparing the efficacy and pregnancy outcome of intrauterine balloon and intrauterine contraceptive device in the prevention of adhesion reformation after hysteroscopic adhesiolysis in infertile women: a prospective, randomized, controlled trial study.

STUDY OBJECTIVE: To evaluate the efficacy and pregnancy outcomes of intrauterine balloon and intrauterine contraceptive devices in the prevention of adhesion reformation following hysteroscopic adhesiolysis in infertile women with moderate to severe intrauterine adhesion. DESIGN: A prospective, randomized, controlled trial study. SETTING: A tertiary university hospital. PATIENTS: A total of 130 patients with moderate (American Fertility Society [AFS] score of 5-8) and severe (AFS score of 9-12) intrauterine adhesions were recruited. INTERVENTIONS: 86 patients were evenly allocated to group treated with an IUD for 1 month and group treated with an IUD for 2 months. 44 patients were allocated to group treated with a Foley catheter balloon.(IUD: Yuangong IUD). MEASUREMENTS AND MAIN RESULTS: The primary outcome measures were the AFS score, endometrial thickness, and pregnancy outcome. After hysteroscopy, the AFS score was significantly decreased(P<0.05), whereas endometrial thickness was significantly increased across the three groups(P<0.001). Notably, the decline in the AFS score in the balloon group was greater than that in the IUD-1-month group and IUD-2-month group(P<0.01), with no significant difference between the IUD groups(P = 0.298). Lastly, In addition, the extent of the increase in endometrial thickness(P = 0.502) and the pregnancy outcomes(P = 0.803) in the three groups were not significantly different. CONCLUSION: Inserting a balloon or placing an IUD for one or two months can effectively lower the risk of adhesion recurrence and restore the shape of the uterine cavity. While the therapeutic effect of the balloon was superior to that of the IUD, no significant differences were observed in the one-month and two-month IUD groups. TRIAL REGISTRATION: This research was registered in the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/enIndex.aspx ); Clinical trial registry identification number: ChiCTR-IOR-17,011,943 ( http://www.chictr.org.cn/showprojen.aspx?proj=17979 ). Date of trial registration: July 11, 2017.

Endometriosis in infertile women: an observational and comparative study of quality of life, anxiety, and depression.

BACKGROUND: A women's chances of getting pregnant decreases in cases of infertility, which may have several clinical etiologies. The prevalence of infertility is estimated as 10-15% worldwide. One of the causes of infertility is endometriosis, defined as the presence of an endometrial gland and/or stroma outside the uterus, inducing a chronic inflammatory reaction. Thus, infertility and endometriosis are diagnoses that significantly affect women's mental health. This study accessed and compared the levels of depression, anxiety, and quality of life in infertile women with and without endometriosis. METHODS: was an observational and cross-sectional study which included 201 infertile women, 81 of whom were also diagnosed with endometriosis. The STROBE Guidelines was used. The data were collected using validated scales: Hamilton D Questionnaire, Beck Depression Inventory, and Fertility Quality of Life Questionnaire; The data were collected at the Ideia Fertil Institute (Santo Andre, Brazil), between February 28 and June 8, 2019. RESULTS: the infertile women with endometriosis reported higher presence of depressive symptoms and a lower quality of life compared to women with infertility only. Similar presence of anxiety symptoms was observed regardless of being diagnosed with endometriosis. Women with infertility and endometriosis presented lower levels in quality-of-life domains when compared to women with infertility only - Mind and Body (58.33 × 79.17, p < 0.001), Relational (75 × 81.25, p = 0.009), Social (66.67 × 77.08, p = 0.001), Emotional (50.62 × 67.43, p < 0.001). CONCLUSION: the findings indicate the need for increased psychosocial support care for women suffering from infertility and endometriosis to assist them in maintaining and managing their own mental health and achieving their reproductive goals.

An Estrogen-NK Cells Regulatory Axis in Endometriosis, Related Infertility, and Miscarriage.

Endometriosis is a common estrogen-dependent condition that impacts 8-10% of women in their reproductive age, resulting in notable pain, morbidity, and infertility. Despite extensive research endeavors, the precise cause of endometriosis remains elusive, and the mechanisms contributing to its associated infertility are still not well comprehended. Natural killer (NK) cells, vital innate immune cells crucial for successful pregnancy, have been investigated for their potential involvement in the pathogenesis of endometriosis. Prior research has mainly concentrated on the diminished cytotoxicity of NK cells in endometrial fragments that evade the uterus. Interestingly, accumulating evidence suggests that NK cells play multifaceted roles in regulating the biology of endometrial stromal cells (ESCs), promoting local immune tolerance, influencing endometrial receptivity, oocyte development, and embryo implantation, thereby contributing to infertility and miscarriage in patients with endometriosis. In this comprehensive review, our goal is to summarize the current literature and provide an overview of the implications of NK cells in endometriosis, especially concerning infertility and pregnancy loss, under the influence of estrogen.

[Fertility, endometriosis and pregnancy planning]. / Fertilité, endométriose et projet de grossesse.

Endometriosis does not always mean infertility, and treatment depends on the couple's prognosis and their wishes. Spontaneous pregnancy remains possible, all the more so if endometriosis treatment is initiated early in the patient's life. Surgery and assisted reproduction are available to couples who wish to have a child.

Reproductive outcomes after vaginal repair of isthmocele: A preliminary study and systematic review of the literature.

OBJECTIVE: Although vaginal repair of isthmocele is an effective and safe surgical option, data on reproductive and obstetrical outcomes are lacking. The aim of this study is to evaluate reproductive outcomes of women undergone vaginal repair of isthmocele. We also systematically reviewed the existent literature to offer a general view of available data. STUDY DESIGN: Retrospective analysis of a database prospectively collected between January 2018 and January 2022 at San Raffaele Hospital, Milan, Italy. We included secondary infertile women with ultrasound documented isthmocele who undergone vaginal repair. Post-surgical clinical, reproductive and obstetric outcomes were recorded. An advanced systematic search of the literature up to January 2023 was conducted. RESULTS: 17 women were included. The mean age of the included patients was 37.2 ± 2.7 years. The median of previous caesarian sections was 1 (1-2). One intra-operative complication (5.9 %) was reported (bladder injury, repaired at the time of surgery). At follow up, bleeding was successfully treated in 8 women (8/10; 80 %). Pregnancy was obtained in 7 women (7/17; 41.2 %): the conception was spontaneous in 4 women (4/7; 57.1 %) and trough assisted reproductive technology in 3 patients (3/7; 42.9 %). The mean time from surgery to pregnancy was 10.8 (±6.7) months. One spontaneous abortion was reported (1/7; 14.3 %), while live birth was achieved in 6 pregnancies (6/7; 85.7 %). All deliveries were by caesarian section at a median gestational age of 37.5 (36-38.25) weeks. No obstetrical complications were reported. At the time of caesarean section, no defects on the lower segment were retrieved. Regarding the systematic research, among the 21 studies screened, only 4 articles were included in the review. Pregnancy rate was around 60-70 % with very few obstetrical complications (0.01 %) such as abnormal placentation or preterm birth. CONCLUSIONS: Vaginal repair of isthmocele is a minimally invasive, safe and effective surgical approach in terms of postsurgical residual myometrium tichness. Systematic review to date has found low-quality evidences on the impact of vaginal surgery in the management of secondary infertility and obstetrics outcomes in women with isthmocele.

Pregravid preparation of women with chronic endometritis in IVF cycles.

OBJECTIVE: Aim: of our study was to improve the pregravid preparation of women with chronic endometritis to develop individual approaches to overcoming infertility, taking into account the state of endometrium. PATIENTS AND METHODS: Materials and Methods: The study included 90 women (main group, n=90), 28 to 38 years with an anatomically normal uterus and chronic endometritis (CE). Patients were divided into 2 groups: group I - 45 women with CE who received conventional treatment; group II - 45 women with CE who received pregravid preparation by subendometrial injections of Platelet-Rich Plasma (PRP). RESULTS: Results: At the first stage of study, the ART statistical reports from 2015 to 2022 were analyzed at the Medical Center of Reproductive Health ≪Damia≫, (Ivano-Frankivsk). Analysis of the vaginal flora parameters before treatment at the first stage revealed the presence of conditionally pathogenic flora in culture from the cervical canal (Candida albicans - 2.4%, Escherihia coli - 4.8%, Staphylococcus epidermidis - 6.2% Enterococcus faecalis - 6.9%), and was evidence of a possible recurrence of inflammation during gestation. In the age category, the groups of patients were homogeneous, with no significant differences by the level of AMH and the level of CD 138. Biochemical pregnancy be present in 20 patients (44.4%) of group I and 28 (62.2%) of group II. Fertility within a year after the end of therapy was restored with the proposed method of therapy in most women (51.1%), in the comparison group this number was 11.1% lower. Pregnancy rate between the groups (I and II) did not differ significantly. The number of live births in group II - 19 births (42.2%) - was 2 times higher than I group (9 (20.0%), P<0.05). The most common complication for women in the comparison groups was early pregnancy loss. Among 18 (40.0%) clinical pregnancies of group I, 8 women (17.8%) had early miscarriage, 1 ectopic pregnancy (2.2%), while in group II clinical pregnancy be present in 23 women (51.1%). The number of terminated pregnancies was two times lower than in the first group (8.9% vs. 17.8%, P<0.05). CONCLUSION: Conclusions: Chronic endometritis is one of the main causes of pregnancy loss after in vitro fertilization. Patients of the second group were treated with the proposed method of subendometrial injections with Platelet-Rich Plasma (PRP), prepared from autologous blood, is an effective method of preparing the endometrium for embryo transfer and can increase the number of live births in patients with chronic endometritis.

Association with pre-pregnancy BMI on early pregnancy loss in infertility patients in first HRT-FET cycles: A retrospective cohort study.

OBJECTIVE: To investigate the association between pre-pregnancy body mass index (BMI) and the early pregnancy loss rate in patients in first hormone replacement therapy-frozen-thawed embryo transfer (HRT-FET) cycles and find the threshold. METHODS: A retrospective cohort study was conducted using a total of 14030 HRT-FET cycles at the Reproductive Center from January 2017 to December 2021. The association of pre-pregnancy BMI on early pregnancy loss rate in patients in HRT-FET cycles was assessed by performing univariate analysis, multivariable logistic regression, curve fitting and threshold effect analysis. RESULTS: There were 2076 cycles of early pregnancy loss, and the pregnancy loss rate was 14.80%. After adjusting for confounding factors, the early pregnancy loss rate of the obese group was significantly higher than that of the normal weight group (P < 0.05). The threshold effect analysis showed that as the pre-pregnancy BMI ranged from 21.2 to 25.8 kg/m2, the early pregnancy loss rate came to the plateau phase at the low level. In addition, when the BMI was ≥ 25.8 kg/m2, the early pregnancy loss rate increased by 3% (aOR = 1.03, P = 0.01) with each 1 kg/m2 increment of BMI. CONCLUSION: The early pregnancy loss rate might achieve a low level when the pre-pregnancy BMI was within the range of 21.2- 25.8 kg/m2. The early pregnancy loss rate would increase when pre-pregnancy BMI is more than 25.8 kg/m2. For patients in HRT-FET cycles, adjusting their pre-pregnancy BMI to the optimal level by following a healthy diet and daily exercise may help to reduce the early pregnancy loss.

Laparoscopic transfundal approach to cervical dilation: a novel treatment for cervical stenosis and cervical factor infertility.

OBJECTIVE: To demonstrate a novel technique used to restore cervical patency in a patient with severe iatrogenic cervical stenosis. DESIGN: Surgical video case report. SETTING: A single academic institution. PATIENT(S): We highlight the case of a 35-year-old nulliparous woman with a history of primary infertility. Her past medical history was significant for focal, invasive, well-differentiated squamous cell carcinoma of the cervix, for which she underwent a loop electrosurgical excision procedure. During her infertility assessment, she was found to have an extremely stenotic cervix that was refractory to conventional treatment options. INTERVENTIONS: This video highlights our innovative laparoscopic transfundal technique used to restore her cervical patency. MAIN OUTCOME MEASURES: None, as this is a descriptive case report. RESULTS: Postoperatively, the patient had continued cervical patency for >1 year with successful fertility treatment resulting in pregnancy. CONCLUSIONS: To our knowledge, this is the first case report describing a laparoscopic transfundal approach used to reestablish cervical patency. This approach may be considered for patients with cervical stenosis who have not responded to standard conservative therapies.

The moderating effect of dietary selenium intake on the risk of infertility-associated depressive symptoms in female.

AIM: To analyze the associations between infertility or dietary selenium intake and depressive symptoms as well as the role of selenium intake on the association between infertility and depressive symptoms in women. METHODS: This study retrieved the data of 4949 women from National Health and Nutrition Examination Survey (NHANES) database. Univariable and multivariable weighted logistic regression analyses were applied to assess the associations of selenium intake or infertility with the risk of depressive symptoms as well as the regulation of selenium intake on the risk of depressive symptoms related to infertility. RESULTS: The elevated risk of depressive symptoms was found in participants with infertility (odds ratio [OR] = 1.54, 95% confidence interval [CI]: 1.11-2.15). The risk of depressive symptoms was reduced in women with selenium intake ≥55 µg (OR = 0.64, 95%CI: 0.46-0.90). Compared with women without infertility who had selenium intake <55 µg, those with infertility and had selenium intake <55 µg were associated with elevated risk of depressive symptoms after adjusting for confounding factors (OR = 2.01, 95%CI: 1.03-3.90). The risk of depressive symptoms was not significantly increased in women with infertility who had selenium intake ≥55 µg in comparison with subjects without infertility who had selenium intake ≥55 µg (p > 0.05). CONCLUSION: Selenium intake regulated the association between infertility and depressive symptoms.

Histologic Remission in Inflammatory Bowel Disease and Female Fertility: A Nationwide Study.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is linked to reduced female fertility, but it is unclear how fertility rates vary by histologic disease activity. METHODS: Nationwide IBD cohort of Swedish women aged 15 to 44 years. We examined fertility rates during periods with vs without histologic inflammation (n = 21,046; follow-up, 1990-2016) and during periods with vs without clinical activity (IBD-related hospitalization, surgery, or treatment escalation) (n = 24,995; follow-up, 2006-2020). Accounting for sociodemographics and comorbidities, we used Poisson regression to estimate adjusted fertility rate ratios (aFRRs) for live births conceived during 12-month periods of histologic inflammation (vs histologic remission) and 3-month periods of clinically active IBD (vs quiescent IBD). RESULTS: During periods with vs without histologic inflammation, there were 6.35 (95% confidence interval [CI], 5.98-6.73) and 7.09 (95% CI, 6.48-7.70) live births conceived per 100 person-years of follow-up, respectively, or 1 fewer child per 14 women with 10 years of histologic inflammation (aFRR, 0.90; 95% CI, 0.81-1.00). In women with histologic inflammation, fertility was similarly reduced in ulcerative colitis (UC) (aFRR, 0.89 [95% CI, 0.78-1.02]) and Crohn's disease (CD) (aFRR, 0.86 [95% CI, 0.72-1.04]). Clinical IBD activity was associated with an aFRR of 0.76 (95% CI, 0.72-0.79) or 1 fewer child per 6 women with 10 years of clinical activity. Fertility was reduced in clinically active UC (aFRR, 0.75 [95% CI, 0.70-0.81]) and CD (aFRR, 0.76 [95% CI, 0.70-0.82]). Finally, among women with clinically quiescent IBD, histologic inflammation (vs histologic remission) was associated with reduced fertility (aFRR, 0.85 [95% CI, 0.73-0.98]). CONCLUSIONS: An association between histologic and clinical activity and reduced female fertility in CD and UC was found. Notably, histologic inflammation was also linked to reduced fertility in women with clinically quiescent IBD.

Do probiotic interventions improve female unexplained infertility? A critical commentary.

Disruption of women's gut and cervicovaginal microbiota has been associated with multiple gynaecological diseases such as endometriosis, polycystic ovary syndrome, non-cyclic pelvic pain and infertility. Female infertility affects 12.6% of women worldwide; its aetiology is complex and multifactorial and can be underpinned by uterine pathologies, systemic diseases and age. In addition, a new perspective has emerged on the role of the gut and vaginal microbiomes in reproductive health. Research shows that the administration of precisely selected probiotics, often in combination with prior antibiotic treatment, may facilitate the restoration of symbiotic microbiota to increase successful conception and assisted reproductive technology outcomes. However, clarity on this issue from fuller research is currently hampered by a lack of consistency and harmonization in clinical studies: various lactobacilli and bifidobacteria species have been delivered through both the oral and vaginal routes, in different dosages, for different treatment durations. This commentary explores the intricate relationship between the microbiota in the cervicovaginal area and gut of women, exploring their potential contribution to infertility. It highlights ongoing research on the use of probiotic formulations in improving pregnancy outcomes, critically examining the divergent findings in these studies, which complicate a conclusive assessment of the efficacy of these interventions.

Comparison of microbial abundance and diversity in uterine and peritoneal fluid in infertile patients with or without endometriosis.

INTRODUCTION: Endometriosis (EM) is a multifactorial disease that affects 10 - 15% of women of reproductive age. Additionally, 30-50% of women with EM suffer from infertility. The mechanism of infertility caused by EM has not yet been consistently explained. In recent years, studies have shown a link between infertility associated with EM and changes in the reproductive tract microbiota. METHODS: In this study, we involved 26 EM patients (8 cases of stage I-II and 18 cases of stage III-IV) and 31 control subjects who were tubal obstruction-related infertility (TORI). The samples from peritoneal fluid (PF) and uterine fluid (UF) were collected and sequenced by 16 S rRNA amplicon. RESULTS: In the comparison of microbial diversity, we found no significant differences in the microbial diversity of PF and UF between patients with stage I-II EM and those with TORI. However, there was a significant difference in microbial diversity among patients with stage III-IV EM compared to the previous two groups. Lactobacillus decreased in PF of EM compared to the control group, while it increased in UF. In PF, the abundance of Pseudomonas, Enterococcus, Dubosiella and Klebsiella was significantly higher in patients with stage III-IV compared to TORI patients. And in UF, the main differences existed between stage I-II EM compared to the other two groups. The abundance of pontibacter, aquabacterium, Rikenellaceae and so on at the genus level was significantly enriched in the EM patients with stage I-II. In the analysis based on KEGG database, EM may affect the receptivity related pathways of the endometrium by influencing changes in the uterine microbiota. CONCLUSION: Our results indicated that as EM progresses, the microorganisms in UF and PF keep changing. These changes in the microbiota, as well as the resulting alternations in gene functional classification, may play an important role in the infertility associated with EM.