The influence of lifestyle interventions and overweight on infertility: a systematic review, meta-analysis, and meta-regression of randomized controlled trials.

This study aimed to investigate the effect of lifestyle intervention (LSI) on diagnosed infertility in overweight and obese women. A systematic review and meta-analysis were conducted. A literature search was performed on the following databases from September 2022 to December 2022: PubMed, Web of Science, and SPORTDiscus. The inclusion criteria were the following: women between 18 and 45 years of age, BMI over 25.0 kg/m2, diagnosed with infertility, a weight loss intervention, and control group part of RCTs. In total, 15 studies were identified and included. The meta-analysis shows a beneficial effect of LSI on reducing weight, waist circumference, and BMI and increasing infertility. A significantly beneficial effect of lifestyle intervention on weight reduction was observed for participants who initially had a higher BMI, while a non-significant effect was observed for individuals with a BMI above 35 kg/m2. The meta-analysis showed a beneficial effect of lifestyle intervention on ovulation incidence and sex hormone-binding globulin. The lifestyle intervention group had 11.23 times more ovulatory incidence than the control group, which in turn increased the ability to conceive. As robust evidence for the effect of lifestyle interventions on infertility in obese and overweight women was found, it is advised to integrate similar interventions into future infertility treatment processes.

Poor Ovarian Response to Gonadotrophins in PCOS Women after Laparoscopic Ovarian Drilling.

Background and Objectives: Polycystic ovary syndrome (PCOS) is a major cause of anovulatory infertility, and ovulation induction is the first-line treatment. If this fails, laparoscopic ovarian drilling (LOD) is used to induce mono-ovulations. There have been implications, that LOD can cause destruction of ovarian tissue and therefore premature ovarian failure. Furthermore, unexpected poor ovarian response (POR) to gonadotrophins can occur in PCOS women after LOD. There have been reports about FSH receptor polymorphisms found in women with PCOS that are related to higher serum FSH levels and POR to gonadotrophins. Materials and Methods: In the present study, we retrospectively analyzed data of 144 infertile PCOS women that had LOD performed before IVF. Results: Thirty of included patients (20.8%) had POR (≤3 oocytes) to ovarian stimulation with gonadotrophins. Women with POR had significantly higher median levels of basal serum FSH (7.2 (interquartile range (IQR), 6.0-9.2) compared to women with normal ovarian response (6.0 (IQR, 5.0-7.4); p = 0.006). Furthermore, women with POR used a significantly higher median cumulative dose of gonadotrophins (1875 IU (IQR, 1312.5-2400) for ovarian stimulation compared to women with normal ovarian response (1600 IU (IQR, 1200-1800); p = 0.018). Conclusion: Infertile PCOS women who experience POR after LOD have significantly higher serum FSH levels compared to women with normal ovarian response after LOD. As these levels are still within the normal range, we speculate that LOD is not the cause of POR. We presume that women with PCOS and POR after LOD could have FSH-R genotypes associated with POR and higher serum FSH levels.

Uterine rupture in pregnancy after hysteroscopic septum resection: a 20-year retrospective analysis.

INTRODUCTION: In this study, we reviewed the cases of uterine rupture in our setting, identified which of them had previously undergone hysteroscopic septum resection (HSR), and evaluated the main clinical characteristics for each case. MATERIAL AND METHODS: We retrospectively analyzed (ClinicalTrial ID: NCT04449640) the delivery outcomes from the National Perinatal Information System of the National Institute of Public Health of the Republic of Slovenia of the last 20 years (1 January 1999 - 31 December 2019) and cross-linked the patients with surgical data from our electronic database. We collected baseline characteristics, surgical details and obstetrical outcomes. We excluded women who had undergone previous myomectomy or cesarean section (CS) and described the clinical course of each case since no statistical analysis was performed. RESULTS: We found four patients who had uterine rupture in pregnancy after HSR. Median time to pregnancy was 17 months (range 1-60), all the women underwent CS and fetal-maternal outcomes were acceptable in half of the cases. Symptoms were nonspecific and included pain, fetal distress and vaginal bleeding. CONCLUSION: Uterine rupture in pregnancy after a previous HSR is a very rare, but life-threatening event. Prompt diagnosis can ensure successful management and avoid adverse maternal-fetal outcomes.

Expression of Markers of Endometrial Receptivity in Obese Infertile PCOS Women before and after the Weight Loss Program-A Preliminary Study.

Obesity is an increasing worldwide problem, and it is common in women with polycystic ovaries syndrome (PCOS). It is well known that women with PCOS have lower chances of spontaneous conception as well as lower success with IVF procedures. The mechanisms by which obesity causes lower fertility are not yet fully understood. The aim of the present study was to determine the effect of a lifestyle intervention weight loss program on the expression of the endometrial genes during the window of implantation (WOI). For this purpose, 15 infertile women with obesity and PCOS were included in the study. Endometrial samples were taken during the WOI before and at the end of the program, and RNASeq analysis was performed. There were no significantly differentially expressed genes before and after the weight loss program. We then compared the results of our study with previously published studies on markers of endometrial receptivity. The biomarker genes that were found to be down-regulated during the WOI in previous studies were more down-regulated after the weight loss program in the present study. Furthermore, 25% of the women who achieved the desired 5% or more weight reduction conceived spontaneously. Our study shows that weight loss might positively impact endometrial receptivity. which may lead towards the improved fertility of obese women with PCOS.

The Impact of COVID-19 Lockdown on Weight Loss Program in Infertile Polycystic Ovary Syndrome Women with Obesity.

INTRODUCTION: Lockdown due to the COVID-19 pandemic has caused gym closures and adjustments to ongoing weight loss programs were needed in order to keep the programs running. Little is known whether adjustments affected the success of weight reduction. Weight reduction of at least 5% is related to improved fertility and better pregnancy outcomes in obese women. This study compared success of the weight loss program in infertile polycystic ovary syndrome women with obesity who attended the program before and during lockdown due to COVID-19 pandemic. Furthermore, we checked whether there were any differences in spontaneous pregnancy rates between both groups at the end of the program. METHODS: Altogether, 27 women were prospectively included to the weight loss program. Twelve women attended the 8 - week program before COVID-19 pandemic. Fifteen women began the program before the lockdown and ended it during lockdown. Due to lockdown, the program was prolonged for 4 weeks and taken online. RESULTS: On average, prior to lockdown women achieved a BMI reduction of 6.8% whereas women that attended the program during the lockdown reduced their BMI for 3.7%. This difference was not statistically significant. No significant differences were seen in other measured anthropometric and endocrine parameters between both groups. Furthermore, there were no differences in spontaneous pregnancy rates between both groups. In women who reduced their BMI for 5% or more, spontaneous pregnancy rate was 29.4%. DISCUSSION/CONCLUSIONS: Although statistical significance has not been reached in the present study, we have shown that lockdown due to COVID-19 pandemic has led to almost half lower BMI reduction despite adaptations and longer duration of the weight loss program. On average, BMI in the group of women that attended the program during lockdown was 3.7% lower after the end of the weight loss program. This means they did not reach the wanted 5% reduction which is known to improve fertility. We have also shown that weight reduction is the correct approach for treating infertile women with obesity, as almost 30% of those who reduced their body weight by 5% or more conceived spontaneously.

Female reproductive potential after oncological treatment: a rare case report of acute myeloid leukemia in monozygotic twin sisters with literature review.

BACKGROUND: Acute myeloid leukemia (AML) in monozygotic twins is a rare event and, until now, only a few cases have been reported. Due to improved oncological treatment and cancer survival rates, quality of life considerations post-treatment have become an important aspect in the treatment regime. The ability to have their own biological children is considered one of the most important indicators of quality of life by cancer survivors. As fertility following oncological treatment is often impaired, fertility preservation methods should be offered to these patients prior to the treatment. Here, we present a very rare case in which we can in vivo observe the impact of oncological treatment on female fertility when applied before and after puberty. CASE PRESENTATION: This is a very rare case of concordant AML in monozygotic twin sisters. Twin A became sick at the age of 21 months. She was treated with cytostatic medications and then underwent bone marrow transplantation (BMT), the donor being her twin sister B. After 27 years, she is disease free and has regular periods. After trying to conceive for 4 years, she was seen by an infertility specialist. She underwent hysteroscopic uterine septum removal and laparoscopic enucleation of bilateral paraovarian cysts. Following those procedures, she immediately conceived naturally. Twin B became sick at 15 years of age. She was treated with chemotherapy and cranial radiation and relapsed after 10 years. She then received chemotherapy and had a BMT. Until relapse, she had normal menstrual cycles. After the second treatment she became amenorrhoeic and is now part of an oocyte donation program. CONCLUSIONS: This is a case of AML in monozygotic twins who, after treatment, have completely different reproductive potential. They both received oncological treatment, and one of them conceived conceived naturally while the other suffered premature ovarian failure and is not able to have a biological child. Based on the outcome of this case, it appears that the pre-pubertal state truly serves as protection against ovarian failure.

PGR and PTX3 gene expression in cumulus cells from obese and normal weighting women after administration of long-acting recombinant follicle-stimulating hormone for controlled ovarian stimulation.

PURPOSE: The present study aimed to determine clinical IVF parameters and gene expression in cumulus cells (CCs) in obese and normal weighting women after administration of 150 mcg of corifollitropin alfa for controlled ovarian hyperstimulation (COH). METHODS: 150 mcg of corifollitropin alfa and gonadotropin releasing hormone antagonist were used for COH. Analysis of CC gene expression was performed using quantitative real-time PCR. RESULTS: We did not find significant differences in biochemical and clinical pregnancy rates between obese and normal weighting women. Obese women required twice as much of additional gonadotropins for ovarian stimulation and had a significantly lower proportion of good quality embryos on day 5 of IVF cycle. Expression of PGR and PTX3 was significantly higher in CCs of obese women. CONCLUSION: Obese women require significantly larger amounts of gonadotropins to achieve similar IVF success rates as normal weighting women. Differences in CC gene expression and smaller proportion of good quality embryos may imply that oocytes derived from obese women are of lower quality. Further studies are needed to evaluate whether obesity itself or the higher amount of gonadotropins used in obese women causes this effect.

Spontaneous pregnancy rates after reproductive surgery.

With the development of IVF procedures, the role of reproductive surgery in the management of infertile couples has been questioned. Pregnancy rates (PR) after IVF procedures are well known, but recent data on spontaneous PR after reproductive surgery are scarce. This study aimed to prospectively evaluate how often fertility is restored by reproductive surgery and to identify which independent factors influence spontaneous pregnancy after reproductive surgery. Eight hundred eighty-eight infertile women who underwent surgery for infertility were prospectively included. Women who were referred to IVF after surgery, ceased to plan pregnancy and were lost to follow-up were excluded. Spontaneous PR was analysed for 519 women. A total of 252 (48.6%) women, including 30 treated with clomiphene citrate, conceived spontaneously in the 12-18 months observation period following surgery. Multivariate logistic regression showed that woman's age (OR 0.95, 95% CI 0.90-0.99) and duration of infertility (OR 0.86, 95% CI 0.74-0.99) significantly influence spontaneous PR. Each year of infertility lowers spontaneous PR following surgery by 14% and each year of woman's age by 5%. The study shows a relatively high percentage of women conceived spontaneously after reproductive surgery. The role of reproductive surgery in the management of infertility should be re-evaluated.

Transcriptomic Analysis and Meta-Analysis of Human Granulosa and Cumulus Cells.

Specific gene expression in oocytes and its surrounding cumulus (CC) and granulosa (GC) cells is needed for successful folliculogenesis and oocyte maturation. The aim of the present study was to compare genome-wide gene expression and biological functions of human GC and CC. Individual GC and CC were derived from 37 women undergoing IVF procedures. Gene expression analysis was performed using microarrays, followed by a meta-analysis. Results were validated using quantitative real-time PCR. There were 6029 differentially expressed genes (q < 10-4); of which 650 genes had a log2 FC ≥ 2. After the meta-analysis there were 3156 genes differentially expressed. Among these there were genes that have previously not been reported in human somatic follicular cells, like prokineticin 2 (PROK2), higher expressed in GC, and pregnancy up-regulated nonubiquitous CaM kinase (PNCK), higher expressed in CC. Pathways like inflammatory response and angiogenesis were enriched in GC, whereas in CC, cell differentiation and multicellular organismal development were among enriched pathways. In conclusion, transcriptomes of GC and CC as well as biological functions, are distinctive for each cell subpopulation. By describing novel genes like PROK2 and PNCK, expressed in GC and CC, we upgraded the existing data on human follicular biology.

Ureteral Injury with Delayed Massive Hematuria after Transvaginal Ultrasound-Guided Oocyte Retrieval.

We report a case of ureteral injury with delayed hematuria after transvaginal oocyte retrieval. A 28-year-old infertile patient with a history of previous laparoscopic resection of endometriotic nodes of both sacrouterine ligaments presented with abdominal pain one day after oocyte retrieval. Four days after oocyte retrieval, she presented with massive hematuria that reappeared 6 days after oocyte retrieval. Monopolar coagulation with wire electrode and insertion of a double-J-stent was performed during operative cystoscopy. The patient recovered completely after transfusion and had no signs of renal impairment after ureteric stent removal. This is the first report of ureteral injury after oocyte retrieval presenting itself with delayed massive hematuria and no signs of renal dysfunction or urinary leakage into retroperitoneal space.

No specific gene expression signature in human granulosa and cumulus cells for prediction of oocyte fertilisation and embryo implantation.

In human IVF procedures objective and reliable biomarkers of oocyte and embryo quality are needed in order to increase the use of single embryo transfer (SET) and thus prevent multiple pregnancies. During folliculogenesis there is an intense bi-directional communication between oocyte and follicular cells. For this reason gene expression profile of follicular cells could be an important indicator and biomarker of oocyte and embryo quality. The objective of this study was to identify gene expression signature(s) in human granulosa (GC) and cumulus (CC) cells predictive of successful embryo implantation and oocyte fertilization. Forty-one patients were included in the study and individual GC and CC samples were collected; oocytes were cultivated separately, allowing a correlation with IVF outcome and elective SET was performed. Gene expression analysis was performed using microarrays, followed by a quantitative real-time PCR validation. After statistical analysis of microarray data, there were no significantly differentially expressed genes (FDR<0,05) between non-fertilized and fertilized oocytes and non-implanted and implanted embryos in either of the cell type. Furthermore, the results of quantitative real-time PCR were in consent with microarray data as there were no significant differences in gene expression of genes selected for validation. In conclusion, we did not find biomarkers for prediction of oocyte fertilization and embryo implantation in IVF procedures in the present study.

Specific gene expression differences in cumulus cells as potential biomarkers of pregnancy.

The development of an objective and accurate test that could help select embryos with the highest chance of achieving pregnancy in IVF procedures is an important goal of reproductive medicine. For this purpose, cumulus cell gene expression is being studied to find biomarkers of pregnancy. Several recent studies have proposed potential biomarkers of pregnancy expressed in cumulus cells; however, these have mostly not been validated on an independent set of samples. The aim of this study was to analyse the expression of EFNB2, RGS2 and VCAN genes proposed as biomarkers of pregnancy in cumulus cells by quantitative polymerase chain reaction. Gene expression was evaluated in 43 individual cumulus cell samples, derived from a highly homogenous group of 43 women. The same protocol for ovarian stimulation was used for all women, and elective single embryo transfer was performed. Expression levels of RGS2 and VCAN did not differ between cumulus cells of implanted and non-implanted embryos. EFNB2 showed borderline higher expression in cumulus cells of non-implanted embryos, which is contradictory to previous studies. Altogether, the results of previous studies in which EFNB2, RGS2 and VCAN were proposed as biomarkers of pregnancy could not be replicated in our set of cumulus cell samples.