Preimplantation Genetic Testing for Aneuploidy in In Vitro Fertilization Using Comprehensive Chromosome Screening: A Systematic Review and Meta-Analysis.

The utility of pre-implantation genetic testing (PGT-A) is controversial, with older meta-analyses demonstrating improved pregnancy outcomes, while newer trials have not shown benefit. Therefore, we performed a meta-analysis which aimed to evaluate the benefits of PGT-A using comprehensive chromosome screening (CCS) and its effects on in vitro fertilization (IVF) outcomes among randomized controlled trials (RCTs). We conducted a systematic search to identify RCTs comparing women undergoing PGT-A with CSS with women not undergoing PGT-A, from inception to December 2020. Random effects meta-analysis was utilized to calculate average odds ratios (OR) for clinical pregnancy rate (CPR), ongoing pregnancy rate (OPR), and miscarriage rate (MR). The heterogeneity of exposure was assessed using Forest plots and I2 statistics. Publication bias was evaluated using Egger's test. Among 1251 citations, seven RCTs met the inclusion criteria. Biopsies of embryos were carried out at various developmental stages, including polar body, day 3, and day 5-6 of culture. Data was analyzed as all studies and blastocyst only. Meta-analysis failed to show improvement in OPRs using PGT-A in the all ages, <35 years old and ≥35 years old age groups. There was also no significant difference in CPRs in any group. The MR decreased with the use of PGT-A (among all biopsy types and among blastocyst biopsies) in the all-ages group, but not when stratifying according to patient age <35 and ≥35 years old. More data regarding the risks and advantages of PGT-A are needed to make a final decision on the value of this intervention in clinical practice. The exact magnitude of the benefit of PGT-A selection cannot be correctly determined until multiple standardized protocol IVF PGT-A trials are conducted.

The Impact of Noncavity-Distorting Intramural Fibroids on Live Birth Rate in In Vitro Fertilization Cycles: A Systematic Review and Meta-Analysis.

What is the impact of noncavity-distorting intramural fibroids on live birth rates in in vitro fertilization (IVF) cycles? We searched Embase, MEDLINE, Google Scholar, Cochrane Library, and PUBMED from inception to May 2018. We included studies with women undergoing IVF treatment who had at least one noncavity-distorting intramural fibroid. The studies had to report one or more of the following outcomes: live birth rate as our primary outcome, and implantation rate, clinical pregnancy rate, or miscarriage rate as our secondary outcomes. We excluded studies where women also had submucosal fibroids or had undergone myomectomy. Two authors independently selected studies and extracted data. Methodological quality was assessed using Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. We included 15 studies with 5029 patients. Patients with noncavity-distorting intramural fibroids had 44% lower odds of live birth (estimated average odds ratio [OR] = 0.56, 95% confidence interval [CI] = 0.46-0.69) and 32% lower odds of clinical pregnancy (estimated average OR = 0.68, 95% CI = 0.56-0.83). Subgroup analysis of women with purely intramural fibroids showed significantly lower odds of live birth rates and clinic pregnancy rates. Analysis of prospective and retrospective studies shows that noncavity-distorting intramural fibroids have a significant adverse effect on live birth rates in women undergoing IVF. Further, well-designed prospective studies are needed to investigate whether removal of these fibroids improves IVF outcomes in this population.

Atherosclerotic cardiovascular disease in women with endometriosis: a systematic review of risk factors and prospects for early surveillance.

Endometriosis and atherosclerotic cardiovascular disease (ASCVD) share similar pathogenic mechanisms. Hence, this systematic review evaluates the association between endometriosis and lifetime ASCVD risk including co-prevalence with dyslipidaemia, atherosclerosis and non-invasive markers of endothelial dysfunction. The electronic databases Embase, PubMed, MEDLINE, Cochrane Register of Trials and ClinicalTrials.gov were systematically searched for relevant articles. Two prospective cohort studies demonstrated an increased lifetime ASCVD risk after controlling for demographic and lifestyle confounders in women with endometriosis, as measured by higher incidence of myocardial infarction (relative risk [RR] 1.52), angiography-confirmed angina (RR 1.91), or requiring coronary artery bypass graft surgery (RR 1.35). Among 10 studies that included 407 patients with surgically proven endometriosis and 557 controls, RR of developing hypercholesterolemia and hypertension were 1.25 and 1.14, respectively, while higher serum lipoprotein a and lower paraoxonase 1 levels were found in women with endometriosis that was negatively correlated with stage of disease (r = -0.74, P < 0.0001). Hence, currently available evidence suggests that women with endometriosis are at higher lifetime risk of developing ASCVD than women without endometriosis. However, robust causal evidence is still lacking and future studies are needed to determine whether women with endometriosis represent a high-risk population for lifelong ASCVD risk.

Association between sperm DNA fragmentation and idiopathic recurrent pregnancy loss: a systematic review and meta-analysis.

Sperm DNA fragmentation (sDF) has emerged as a valuable tool for evaluating male fertility, yet the relationship between DNA fragmentation in the male gamete and idiopathic recurrent pregnancy loss (RPL) remains a topic of ongoing debate. Hence, a meta-analysis was conducted of 12 prospective and 2 retrospective studies involving 530 men with a history of RPL who underwent sDF testing compared with 639 fertile control participants. The main outcome measures were sDF measured by comet assay, TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end labelling (TUNEL), sperm chromatin dispersion (SCD) or sperm chromatin structure assay. Overall, couples with a history of idiopathic RPL demonstrated higher levels of sDF than fertile couples (average mean difference 11.98, P < 0.001). Subgroup analysis demonstrated a similar average mean difference between the RPL and control groups using SCD compared with TUNEL, while mean paternal age and mean sperm motility in the RPL groups tested by meta-regression demonstrated no significant effect on the mean differences in sDF (P > 0.10). These results support the diagnostic value of sDF over standard semen analysis, as well as a possible paternally derived genetic origin of unexplained RPL. Further prospective studies are required to further assess the predictive utility of sDF for assessing couples with unexplained RPL.

Link between Endometriosis, Atherosclerotic Cardiovascular Disease, and the Health of Women Midlife.

Endometriosis and atherosclerotic cardiovascular disease (ASCVD) are both essentially diseases of inflammation. It is well established that inflammation is the leading mechanism in the initiation and maintenance of vascular injury and in the development and progression of atherosclerosis. Thus, if women with endometriosis do indeed have increased general inflammation, they are at increased risk of developing microvascular dysfunction and atherosclerosis. Currently available evidence suggests that young female patients with proven endometriosis may be at a higher lifetime risk of developing cardiovascular disease; this may be unrecognized due to the relatively young age of women found to have endometriosis. Other mechanisms proposed to explain the link between endometriosis and ASCVD include similarities in the genetic underpinnings of each condition, including microRNA dysfunction and the association between endometriosis and early menopause, a risk for developing ASCVD. Although physicians today primarily focus on traditional risk factors when evaluating an individual female patient's risk of developing ASCVD, we believe that a history of endometriosis should be included as a possible risk factor and needs further exploration. A better understanding of the mechanisms linking endometriosis with ASCVD will hopefully guide the implementation of new therapies to mitigate the increased cardiovascular disease burden that patients with endometriosis might face.

Live Birth Rate after Surgical and Expectant Management of Endometriomas after In Vitro Fertilization: A Systematic Review, Meta-Analysis, and Critical Appraisal of Current Guidelines and Previous Meta-Analyses.

Controversy exists regarding surgical management of endometriomas in infertile women before in vitro fertilization (IVF) because growing evidence indicates that surgery may impair the ovarian response. The objective of the present systematic review and meta-analysis was to compare surgical and expectant management of endometriomas regarding IVF outcomes. Prospective and retrospective controlled studies were found via the Cochrane Library, Embase, and MEDLINE databases. Thirteen studies (1 randomized controlled trial and 12 observational studies, N = 2878) were pooled, and similar live birth rates were observed in the surgically and expectantly managed groups (odds ratio = 0.83; 95% confidence interval [CI], 0.56-1.22; p = .98). The clinical pregnancy rates (odds ratio = 0.83; 95% CI, 0.66-1.05; p = .86), the number of mature oocytes retrieved, and the miscarriage rates were not statistically different between study groups. However, the total number of oocytes retrieved was lower in the surgery group (mean difference = -1.51; 95% CI, -2.60 to -0.43; p = .02). Findings suggest that surgical management of endometriomas before IVF therapy yields similar live birth rates as expectant management. However, future properly designed randomized controlled trials are warranted.

Does preimplantation genetic diagnosis improve reproductive outcome in couples with recurrent pregnancy loss owing to structural chromosomal rearrangement? A systematic review.

Recurrent pregnancy loss (RPL) is a common, yet elusive, complication of pregnancy. Among couples at high risk of RPL, such as those carrying a structural chromosomal rearrangement, preimplantation genetic diagnosis (PGD) has been proposed as a tool to improve live birth rates and reduce the incidence of miscarriage; however, no clear consensus has been reached on its benefits in this population. This systematic review summarizes existing published research on the effect of PGD on pregnancy outcomes among carriers of chromosomal abnormalities with RPL. A comprehensive search of common databases was conducted, which yielded 20 studies. Meta-analysis was precluded owing to significant heterogeneity between studies. The primary outcome of interest was live birth rate (LBR), and a pooled total of 847 couples who conceived naturally had a LBR ranging from 25-71% compared with 26.7-87% among 562 couples who underwent IVF and PGD. Limitations of the study include lack of large comparative or randomized control studies. Patients experiencing RPL with structural chromosomal rearrangement should be counselled that good reproductive outcomes can be achieved through natural conception, and that IVF-PGD should not be offered first-line, given the unproven benefits, additional cost and potential complications associated with assisted reproductive technology.

Reproductive Outcomes after Fertility-Sparing Surgery for Focal and Diffuse Adenomyosis: A Systematic Review.

Among the variety of treatment options to improve reproductive outcomes for infertile women with adenomyosis (AD), uterine-conserving surgery has shown varying success. Hence, we conducted a systematic review around the topic of fertility-sparing surgery across 18 studies and 1396 infertile women with focal and diffuse AD. Patients with focal AD showed mean pregnancy and miscarriage rates of 52.7% (range,14.3%-77.5%) and 21.1% (range, 0%-44.4%), respectively, whereas patients with diffuse AD had mean pregnancy and miscarriage rates of 34.1% (range, 9.4%-100%) and 21.7% (range, 12.5%-33.3%), respectively. Uterine rupture and preterm birth were observed in 6.8% (3/44) and 4.5% (2/44) of pregnant patients with diffuse AD versus 0% (0/35) and 10.9% (12/110) of patients with focal AD, respectively. No significant differences were observed between natural conception versus assisted reproductive technology (ART) with or without gonadotropin-releasing hormone agonist pretreatment. Overall, patients with focal AD appeared to have higher pregnancy rates after conservative surgery compared with diffuse AD, whereas a higher incidence of uterine rupture was reported after surgery for diffuse AD. However, significant heterogeneity precludes any direct comparison, and prospective controlled trials are required to further elucidate the benefits of fertility-preserving surgery over medical or expectant management for AD-related infertility. In view of the debatable benefits of conservative surgery and the possible increase in adverse pregnancy outcomes, particularly in cases of diffuse AD, clinicians should consider surgery on a case-by-case basis because it may be appropriate for women with concurrent AD-associated pelvic pain or menorrhagia, younger infertile women who have failed medical management or older women with infertility despite ART, and those with a history of recurrent pregnancy loss or implantation failure.

Intravaginal misoprostol alone versus intravaginal misoprostol and extraamniotic Foley catheter for second trimester pregnancy termination: an observational study.

BACKGROUND: No systematic empirical research exists addressing the question of optimal pregnancy termination method in second trimester pregnancies. OBJECTIVES: The purpose of this study was to determine the efficacy and safety of intravaginal misoprostol and extraamniotic Foley catheter combination for second trimester pregnancy termination. METHODS: A single center observational study was conducted in a total of 91 pregnancies. Women who met the termination of pregnancy criteria due to feto-maternal indications between 13 to 26 gestational weeks were included into the study. Study participants received intravaginal misoprostol in combination with Foley catheter (n = 46) or intravaginal misoprostol alone (n = 45). RESULTS: The efficacy of intravaginal misoprostol and Foley catheter insertion combination was comparable to that of intravaginal misoprostol alone in terms of time to abortion/birth [median (95% Confidential Interval [95% CI]): 14.33 (11.33-17.25) hours and 12.08 (9.50-15.33) hours, respectively Hazard Ratio: 0.73, 95% CI: 0.47 to 1.12, p = 0.14 (log-rank)]. The only serious maternal event was uterine rupture observed in one woman in Foley combination group. CONCLUSION: The combination of intravaginal misoprostol and extraamniotic Foley catheter for second trimester pregnancy termination does not provide additional efficacy.

Comparison of hysterosalpingography and transvaginal hydrolaparoscopy in patients with tubal factor infertility: a prospective cohort study.

AIM: To evaluate the usefulness, diagnostic accuracy, and cost-effectiveness of transvaginal hydrolaparoscopy (THL) in infertile women with abnormal hysterosalpingogram (HSG) results without obvious pelvic pathology. MATERIAL AND METHODS: THIRTY INFERTILE WOMEN (AGE: 20-40 years) who had tubal pathology in HSG were enrolled in the study. All patients underwent THL instead of standard laparoscopy. A cost analysis was performed comparing HSG and THL methods. RESULTS: In comparison of the HSG of cases by considering the chromopertubation results by THL, the sensitivity and specificity of HSG were 85.1% and 56%, respectively. The reasons for preferring standard laparoscopy rather than THL were: failure in accessing of Douglas (n = 3), insufficient monitoring of pelvis (n = 1), hydrosalpinx (n = 1), and intense peritubal adhesion (n = 1), which were 10%, 3%, 3%, and 3%, respectively. The complication rate was 3.8%. Cost analysis of the procedures showed that the total cost of the THL group was 34.8% lower than the HSG group. CONCLUSIONS: In the elective patients group, THL is more feasible than HSG. Transvaginal hydrolaparoscopy is effective, simple and safe, avoiding the cost, possible complications, time and postoperative patient discomfort compared to conventional laparoscopy.

Comparison of intravaginal progesterone gel and intramuscular 17-α-hydroxyprogesterone caproate in luteal phase support.

The main objective of this study was to compare the pregnancy rates of intramuscular (IM) 17-α-hydroxyprogesterone caproate (17-HPC) and intravaginal (IV) progesterone gel administration in in vitro fertilization-embryo transfer (IVF-ET) cycles. The IM 17-HPC and IV progesterone groups included 632 (66.4%) and 320 (33.6%) women undergoing the first cycles of IVF-ET treatment, respectively. Multivariate analyses annotated for all potential confounders showed that the use of IV progesterone retained a predictive value for the total ß-human chorionic gonadotropin (hCG) positivity and clinical pregnancy rates [adjusted odds ratio (OR), 1.97; 95% confidence interval (CI), 1.28-3.03; P=0.002; and OR, 1.66; 95% CI, 1.07-2.60; P=0.03, respectively]. However, biochemical and on-going pregnancy rates did not differ significantly between the groups (OR, 1.85; 95% CI, 1.00-3.41; P=0.05; and OR, 1.43, 95% CI, 0.89-2.30; P=0.14, respectively). Luteal phase support (LPS) with IV progesterone gel in comparison with IM 17-HPC appears to be associated with higher clinical pregnancy rates in IVF-ET cycles. However, this benefit is clinically irrelevant in terms of on-going pregnancy outcomes.

The use of vascularized jejunum flap for vaginal reconstruction: clinical experience and results in 22 patients.

The ideal reconstructive method for a vagina should provide a durable, stable coverage, a patent tube passage for sexual intercourse, and a natural esthetic contour, while simultaneously minimizing morbidity in both the recipient and donor sites, and should be a single stage procedure obviating the use of stents, obturators, and lubrication. Twenty-two patients with absence of the vagina underwent vaginal reconstruction using the jejunal segment transfer technique. Two flaps required re-operation due to venous compromise postoperatively. The flaps were salvaged with venous anastomosis revisions. The overall flap success rate was thus 100%. No urinary tract or gastrointestinal system complication was observed in any case, nor any instance of vaginal introitus. The average follow-up period was 19 months (between 3 and 48 months). Both the depth and diameter of the neovagina were satisfactory postoperatively. After the immediate postoperative period, the only major and embarrassing problem was hypersecretion of the jejunal segment, but this gradually diminished, especially after the first 3 months. Those patients who engaged in sexual intercourse reported good patency and had no complaints in that regard. In conclusion with its evident advantages, the jejunal segment can serve as a reliable option for vaginal reconstruction. It provides quite satisfactory results from both the cosmetic and functional points of view.

Effects of hormone replacement therapy on bone mineral density in Turkish patients with or without COL1A1 Sp1 binding site polymorphism.

AIM: To evaluate the effects of hormone replacement therapy (HRT) on bone mineral density (BMD) in patients with or without COL1A1 Sp1 binding site polymorphism. METHODS: Non-smoking otherwise healthy postmenopausal women (n=111), who had not received any kind of HRT for at least 3 years (between 2002 and 2005) at the onset of menopause, were included. All patients received 0.625 mg conjugated estrogen/2.5 mg medroxyprogesterone for 18 months. BMD by dual X-ray absorptiometry was measured at the lumbar spine and the femur neck initially and after 18th months of treatment. COL1A1 Sp1 binding site polymorphism was studied using the PCR-RFLP method. RESULTS: After having the results of COL1A1 Sp1 binding site polymorphism, 79 (71.2%) patients were SS, 30(27.0%) were Ss and two (1.8%) were homozygous for ss. The mean age, weight and length of menopausal period were similar between the SS and Ss patients. The Ss heterozygotes had lower BMD values both at the lumbar spine and at the femur neck compared with the SS patients. This difference was also reflected in post treatment measurements. The increase in BMD scores was higher in the SS homozygotes than in the Ss patients. CONCLUSION: Our preliminary data supports the fact that HRT had a lower increase in BMD scores following 18 months of treatment in COL1A1 s allele individuals compared with normal SS individuals. Therefore our study may provide evidence that the Sp1 polymorphism may ameliorate the effects of HRT on BMD, suggesting some additional regimens may be used to support bone strength and to decrease osteoporotic fractures.

Stage I small cell carcinoma of the endometrium: survival and management options.

Small cell carcinoma (SCC) of the endometrium is a rare but aggressive disease with early systemic involvement. Patient survival is short. To date, no effective treatment protocol has been established. Surgery, radiotherapy, and chemotherapy have been used either alone or in combination. The case of a patient with stage IB endometrial SCC is presented with an overview based on all reported cases of SCC of the endometrium and its treatment with particular reference to stage I cases.

Comparison of the long-term histopathologic and morphologic changes after endometrial rollerball ablation and resection: a prospective randomized trial.

STUDY OBJECTIVE: To compare long-term histologic features of endometrial rollerball ablation versus resection. DESIGN: Randomized clinical trial (Canadian Task Force classification I). SETTING: Akdeniz University School of Medicine. PATIENTS: Women with menorrhagia undergoing endometrial ablation. INTERVENTION: Comparison of patients with menorrhagia undergoing endometrial resection and ablation. MEASUREMENTS AND MAIN RESULTS: Endometrial rollerball ablation (n = 23 women) and resection (n = 25) were followed by second-look office hysteroscopy with endometrial biopsy. Mean follow-up to second look hysteroscopy after rollerball ablation and loop resection was 33.4 +/- 2.1 and 31.1 +/- 2.6 months, respectively. Complete atrophy and partial adhesion or obliteration of the cavity and fibrosis were observed at second-look hysteroscopy and were similar in both groups. Whereas all random biopsy specimens after both ablation and resection revealed diminished endometrial glands with varied necrosis and scarring, the number of endometrial glands per field was not correlated with amount of bleeding or menstrual pattern. Bleeding patterns were similar between the groups. No precancerous or malignant lesion was found after the procedures. CONCLUSION: Although efficacy of both endometrial ablation and resection is related to initial thermal destruction and correlated with postablation hysteroscopic and histologic findings, endometrial regrowth may be expected and is not a failure of ablation. Both procedures revealed histopathologically and clinically similar results.

Role of laparoscopic uterine artery coagulation in management of symptomatic myomas: A prospective study using ultrasound and magnetic resonance imaging.

STUDY OBJECTIVE: The aim of this study was to evaluate the efficacy of laparoscopic uterine artery coagulation (LUC) in symptomatic myomatous patients. DESIGN: Prospective study (Canadian Task Force classification II). SETTING: Tertiary care center PATIENTS: Twenty-one women with myomatous uteri. INTERVENTIONS: Laparoscopic uterine artery coagulation. MEASUREMENTS AND MAIN RESULTS: Laparoscopic uterine artery coagulation for myoma was performed by three-puncture laparoscopy, and the difference in uterine and/or myoma volume was determined every 3 months for 12 months clinically and using ultrasonographic and MRI calculations of uterine volume. In addition, pre and postprocedure uterine Doppler indices were determined. Main outcome measures were symptomatic improvement after LUC and reduction in volume calculated by ultrasonography and magnetic resonance imaging (MRI). All treated women reported less bleeding after treatment. At 12 months, a 57% reduction in bleeding was seen in these patients. The mean postoperative pictorial blood loss assessment was significantly lower at 12 months: 303 +/- 30.4 mL (95% CI 284-328) baseline versus 173.5 +/- 17.8 mL (95% CI 164-184) after treatment, p < .05. Postoperative pain was documented in all the patients with a visual analog scale, with a mean of 1.6 cm recorded. The mean reduction in uterine volume (pre- to post-LUC) was 195 +/- 24.3 cm3 (range 89-438). The mean operating time was 52.1 +/- 7.2 minutes (95% CI 49.8-55.4), and the mean estimated blood loss was 65.2 +/- 11.8 dL (95% CI 59.6-70.8). Mean hospitalization time was 32.3 +/- 6.6 hours (95% CI 29.2-35.4). The complication rates were low with the procedure (fever, infection). No patient required hysterectomy due to complications. Ninety percent of the women were satisfied with the procedure. CONCLUSION: Laparoscopic uterine artery coagulation is effective in the management of symptomatic myomas, reducing bleeding and the volume of both uterus and myomas as documented by ultrasonography and MRI. Laparoscopic uterine artery coagulation is a cost-effective and low-morbidity option compared with conventional approaches such as myomectomy or hysterectomy. If the patient's predominant complaint is the feeling of a mass and/or bleeding, alternative treatment options should be explored. The results of this study are encouraging, but more research is needed to validate the cost-effectiveness and long-term results.

Triploidy in a growth discordant twin pregnancy after intracytoplasmic sperm injection treatment. Case report.

OBJECTIVE: We report on a case of a triploidy in one fetus of a twin pregnancy who presented with the findings of growth discordance. METHODS: Three weeks' difference between fetuses in ultrasonographic measurements in the first trimester was observed in a twin pregnancy following intracytoplasmic sperm injection (ICSI) treatment for male infertility. Hydrocephaly developed in the growth-discordant fetus subsequently. Amniocentesis for both fetuses and selective feticide for the abnormal one was performed at 19 weeks' gestation through a single insertion. Fetal karyotype of the abnormal one was 69,XXX and the healthy one was 46,XX. CONCLUSION: Early developed growth discordance in a twin pregnancy may be a sign of chromosomal abnormality such as triploidy. Those cases should be karyotyped without delay to decrease preterm delivery risk of possible selective feticide.