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We aimed to examine the impact of maternal hypothyroidism on placental pathology and perinatal outcomes in singleton live births resulting from IVF, using medical records of IVF births between 2009 and 2017 at a tertiary hospital. The primary outcomes included anatomical, inflammation, vascular malperfusion, and villous maturation placental features. Secondary outcomes included foetal, maternal, perinatal, and delivery complications. There were 1,057 live births, of which 103 (9.7%) and 954 (90.3%) were in the study and control groups, respectively. Patients in the study group were more likely to have diabetes mellitus, polycystic ovarian syndrome, gestational diabetes mellitus, and non-reassuring foetal heart rate (NRFHR) tracing during delivery. After adjustment for potential confounding factors, hypothyroidism was significantly associated with the bilobed placenta (aOR 4.1; 95% CI 1.2-14.3), retroplacental haematoma (aOR 2.4; 95% CI 1.2-4.9), decidual arteriopathy (aOR 2.0; 95% CI 1.2-4.1) and subchorionic thrombi (aOR 2.4; 95% CI 1.3-5.0). Additionally, there was a statistically significant relationship with NRFHR tracing. The incidence of acute chorioamnionitis and severe foetal inflammatory response was higher in the study group. In conclusion, the placental histopathology patterns of singleton IVF live births show that maternal hypothyroidism has a significant impact on adverse perinatal outcomes.

Objective To determine feasibility and accuracy of post-hysteroscopic transvaginal ultrasonography (TVUS) measurement of pelvic fluid accumulation as a screening method for tubal patency (TP). Methods We conducted a retrospective cohort study of 85 patients who underwent uterine cavity assessment by office hysteroscopy at our university-affiliated fertility centre from November 2019 to October 2020. During the study period, two-dimensional (2D) TVUS was performed pre- and post-hysteroscopy to evaluate TP. Patient records were reviewed for demographics, diagnosis, and prior/subsequent TP testing. Predictive values for TP were calculated. Results Pelvic fluid accumulation post-hysteroscopy was found in 65.9% of patients (56). Accumulation of fluid was seen with the use of as little as 10–50 mL of saline. Using more fluid did not increase the likelihood of demonstrating TP (P = 0.17). A trend towards more false-negative results for TP was observed when less fluid was used (7.7% with 10–50 mL vs. 3.8% with 60–190 mL and 1.3% with 200–760 mL; P = 0.10). The positive predictive value (PPV) of TVUS post-hysteroscopy in comparison to known patency/occlusion was 100%; negative predictive value (NPV) was 33%; sensitivity was 82.8%; and specificity was 100%. Similar values were seen in a second analysis that included patients with highly suspected patent or occluded tubes (n = 60); presumed predictive values were: PPV 100%, NPV 42%, sensitivity 78.8%, and specificity 100%. The use of more fluid did not increase pain (P = 0.75). This finding remains after accounting for confounders (e.g., pre-medication, endometrial biopsy). Conclusion TVUS pre- and post-hysteroscopy is feasible in an outpatient setting, and can serve as a reliable screening tool for TP. When hysteroscopy is performed and TP is not known, TVUS can be added for screening, potentially omitting the need for more invasive examinations. With limited non-urgent ambulatory services, it is of upmost importance to maximize information from a single procedure.

This study aimed to study whether IVF stimulation that results in one or two mature follicles should proceed to oocyte retrieval. This is a retrospective cohort study conducted at McGill University Health Center on 459 patients who underwent IVF treatment between 2011 and 2014, undergoing hormonal stimulation and monitoring of their ovarian response. The primary outcomes were pregnancy and live birth rates. Statistical modeling was used to determine individual roles of patient age and ovarian reserve on outcomes, while controlling for the other factors. Of the 459 cycles included in the study, 360 cycles (78.4%) ended in embryo transfer. Live birth rates per cycle were 15.6%, for the ≤ 34-year-olds; 6.5%, for the 35-39-year-olds; and 2.7%, for the ≥ 40-year-olds (p 11 had 56% live birth rate, while those with AFC ≤ 11 had only 6% of live birth rate. This study supports a shift in reasoning from age being the predictor of outcomes in women with a low response at IVF to both age and ovarian reserve needing to be taken into consideration.

Objective To evaluate the effect of embryo stage at transfer on placental histopathology and perinatal outcome in singleton live births resulting from fresh embryo transfers (ETs). Design Retrospective cohort study. Setting Not applicable. Patient(s) The study population included all live births after fresh ETs during the period from 2009 to 2017. Intervention(s) None. Main Outcome Measure(s) Primary outcomes included anatomic, inflammatory, vascular malperfusion, and villous maturation placental features. Secondary outcomes included fetal, maternal, and perinatal complications. Result(s) A total of 677 live births were included in the final analysis and were allocated to the cleavage-stage (n = 252) and blastocyst (n = 425) ET groups. After the adjustment for confounding factors, the blastocyst group was found to be associated with a higher incidence of circummarginate membranes insertion (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.2–3.4), delayed villous maturation (OR 8.5, 95% CI 1.2–69.3), chorangiosis (OR 2.0, 95% CI 1.2–3.8), parenchymal calcifications (OR 10.6, 95% CI 1.4–80.2), and intrapartum nonreassuring fetal heart rate tracing (OR 2.4, 95% CI 1.3–4.5). Compared with cleavage-stage ETs, live births resulting from the blastocysts were associated with a lower incidence of velamentous cord insertion (OR 0.5, 95% CI 0.3–0.9), retroplacental hematoma (OR 0.3, 95% CI 0.1–0.8), subchorionic thrombi (OR 0.3, 95% CI 0.1–0.8), and avascular villi (OR 0.2, 95% CI 0.03–0.7). Conclusion(s) Live births resulting from fresh cleavage-stage and blastocyst ETs have different placental histopathology features, with a higher rate of intrapartum nonreassuring fetal heart rate tracing in the blastocyst group.

PURPOSE: The aim of this study was to determine how female age at the end of the reproductive spectrum effects success of natural cycle intrauterine insemination (IUI) or IUI in combination with ovarian stimulation. METHODS: We performed a retrospective cohort study of women 43 years of age and older at the time of IUI in a single academic fertility center between January 2011 and March 2018. Primary outcomes were both pregnancies and live births per cycle of IUI. Data are presented as percentage or mean ± SD. Fisher exact and chi-squared analyses were performed. RESULTS: There were 9334 IUI cycles conducted during the study period. Of these cycles, 325 IUIs (3.5%) were for women aged 43 years and over at the time of insemination (43.6 ± 0.8, range 43 to 47 years). Analysis of these 325 IUI cycles revealed 5 biochemical pregnancies (1.5%) and only 1 live birth (0.3%). The pregnancy rate did not differ between IUIs using donor sperm (N = 1/49, 2.0%) compared to IUIs with partner sperm (N = 4/276, 1.4%). The pregnancy rate did not differ between IUIs with gonadotropins (N = 2/211, 0.9%), clomiphene or letrozole (N = 2/78, 2.6%), or natural cycle (N = 1/36, 2.8%). CONCLUSIONS: The use of intrauterine inseminations in women 43 years of age and older is an ineffective treatment strategy. This is irrespective of the use of ovarian stimulation or donor sperm. Costly gonadotropin injections did not increase the chance of pregnancy nor did oral medication when compared to natural cycle IUIs.

STUDY QUESTION How does age affect various semen parameters? SUMMARY ANSWER For most semen parameters, the nomogram of the entire population was biphasic, peaking around the fourth decade of life. WHAT IS KNOWN ALREADY In clinical practice, semen quality is examined by using the WHO 2010 reference limits but these limits do not account for male age. A percentile-based, large-scale nomogram describing how different semen parameters change throughout reproductive life has been lacking. STUDY DESIGN, SIZE, DURATION A retrospective study was conducted with 12 188 sperm samples, obtained from individuals who attended the McGill University Health Centre reproductive clinic between 2009 and 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS One sample from each individual who attended the clinic during the study period was analysed by using computer-assisted sperm analysis (CASA). The analysed parameters were human-verified and included sperm concentration, motility, progressive motility, total count, morphology and semen volume. Based on this analysis, the entire dataset (n = 12 188) was further divided into two groups of samples: samples that surpassed the WHO 2010 lower reference limits (‘above reference limits’ group, ARL; n = 6305), and samples that did not (‘below reference limit’ group, BRL; n = 5883). Regression quantiles were fitted as a function of age to generate age-dependent nomograms, and these quantiles were divided into 5th, 25th, 50th, 75th and 95th percentiles. MAIN RESULTS AND THE ROLE OF CHANCE In the entire dataset, age had a significant influence (P LIMITATIONS, REASONS FOR CAUTION First, the semen samples were obtained from individuals who were referred to a fertility clinic, such that the entire dataset does not necessarily represent the general population. Second, the cross-sectional sampling design increases variance, and the nomograms are less accurate in the 5th and 95th percentiles and at the extremes of the age distributions. Third, the observed age-dependent changes in semen parameters do not necessarily indicate changes in fertility, as not all factors that affect male fertility were analysed. Fourth, some of our semen analyses employed CASA, which can have variability issues. Finally, our models did not incorporate possible secular trends. WIDER IMPLICATIONS OF THE FINDINGS We provide the first nomogram that correlates age with semen quality parameters in different population percentiles, thus complementing the current reference limits set by the WHO in 2010. Most examined semen parameters in our study changed non-linearly with age; therefore, age should be regularly employed as a factor in the clinical analysis of semen samples. STUDY FUNDING/COMPETING INTEREST(S) The authors have not received any funding to support this study. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A.

Objective To determine whether 2 months of pretreatment with 5 mg of letrozole daily plus leuprolide acetate at 3.75 mg monthly in women with laparoscopically confirmed American Society of Reproductive Medicine stage I–II endometriosis improves in vitro fertilization (IVF) outcomes. Design Prospective cohort study. Setting University-affiliated tertiary hospital. Patient(s) Women with laparoscopically confirmed endometriosis treated in the period from 2012 to 2016. Intervention(s) None. Main Outcome Measure(s) Primary outcomes: clinical pregnancy and live-birth rate; secondary outcomes: stimulation parameters and pregnancy. Result(s) A total of 68 patients were included in the final analysis. Thirty-six women received a gonadotropin-releasing hormone (GnRH) agonist and an aromatase inhibitor (AI), and 32 women received a GnRH agonist alone. The women did not differ in mean age, antral follicle count, basal serum level of follicle-stimulating hormone, or previous pregnancies. The stimulation parameters were similar between both groups: gonadotropin dose, number of collected oocytes, number of blastocysts. All women underwent a single blastocyst transfer. The grade of embryos transferred did not differ. Clinical pregnancy (24 [66.7%] vs. 13 [40.6%]) and live-birth (22 [61.1%] vs 10 [31.3%]) rates improved with aromatase inhibitor added to the GnRH agonist treatment versus a GnRH agonist alone. Conclusion(s) In this study, we present the first comparison in the medical literature comparing IVF outcomes in women with minimal and mild endometriosis pretreated with a GnRH agonist with or without an AI. This prospective cohort study suggests that combining these two treatment modalities which work at different sites may improve pregnancy outcomes with IVF treatment.

To assess the effects PCOS on live birth rates when transferring a single fresh ideal blastocyst. A retrospective cohort study performed at the university-affiliated reproductive center. Women with PCOS and a control group of normal ovulatory women who underwent their first fresh embryo transfer with single ideal grade blastocyst were included in the study. Demographic, stimulation information and pregnancy outcomes were collected and analysed. The primary outcome was live birth rates, and secondary outcomes included pregnancy and clinical pregnancy rates. 71 Women with PCOS and 272 normal ovulatory controls underwent their first embryo transfer and met the inclusion and exclusion criteria. PCOS patient were younger (31.0 ± 3.7 vs. 33.1 ± 3.2, p = 0.0001), with higher AFC (40.0 ± 9.3 vs. 13.3 ± 4.6, p = 0.0001), required lower dose of gonadotropins to stimulate (1198 ± 786 vs. 1891 ± 1224, p = 0.0001), and had higher serum testosterone levels (2.3 ± 0.7 vs. 1.1 ± 0.3, p = 0.0001). No significant difference was found between the two groups regarding the number of previous pregnancies, the number of previous full-term pregnancies, the level of basal serum FSH, estradiol level at triggering and the BMI. When compared by Chi squared testing pregnancy rates, clinical pregnancy rates and live birth rates did not differ. However, when controlling (with multivariate stepwise logistic regression) for confounders, live birth rates were lower among the women with PCOS (p = 0.035, CI: 0.18−0.92). After controlling for confounders, when transferring a fresh single ideal blastocyst, live birth rates were lower among the women with PCOS than normal ovulatory controls.

PURPOSE: To evaluate fertility preservation outcomes in breast cancer women with different hormonal receptor profiles before oncological treatment. METHODS: The study population included women with a diagnosis of breast cancer who underwent fertility preservation from 2009 until 2018 at a university-affiliated tertiary hospital. Stimulation parameters and fertility preservation outcomes were compared among the following receptor-specific profile groups: (1) estrogen receptor positive (ER+) versus estrogen receptor negative (ER−), (2) triple-negative breast cancer (TNBC) versus estrogen and progesterone receptor positive (ER+/PR+), and (3) TNBC versus non-TNBC. Primary outcome was the total number of mature oocytes. Secondary outcomes included the number of retrieved oocytes, the peak estradiol level, and the number of follicles > 14 mm on the final oocyte maturation trigger day. RESULTS: A total of 155 cycles were included in the final analysis. These were divided into the exposure groups of ER+ (n = 97), ER− (n = 58), ER+/PR+ (n = 85), TNBC (n = 57), and non-TNBC (n = 98). Cycle outcomes revealed similar number of retrieved oocytes and follicles > 14 mm on the trigger day. Women with TNBC had significantly lower number of mature oocytes compared with those with ER + PR+ (7 (5–11) versus 9 (7–15); p = 0.02) and non-TNBC (7 (5–11) versus 9 (7–16); p = 0.01) status. Triple-negative breast cancer profile was associated with a significant reduction in the chance of developing over 10 mature oocytes (OR 0.41; 95% CI 0.19–0.92). CONCLUSION: Among the different hormonal receptor profiles in breast cancer, the TNBC subtype has a negative effect on fertility preservation outcomes.

Study question What is the predictive value of ovarian reserve evaluation in patients with non-iatrogenic primary ovarian insufficiency (NIPOI) for follicle detection in ovarian tissue harvested for cryopreservation? Summary answer Ovarian tissue cryopreservation (OTCP) should be considered if patients present at least one of the following parameters: detectable AMH, FSH≤20mIU/ml, detection of ≥ 1 antral follicle. What is known already In pre-pubertal girls suffering from NIPOI, which majorly has a genetic etiology, fertility preservation using OTCP is commonly practiced. When OTCP was performed in an unselected group of children and adolescents with NIPOI, only 26% of them had follicles in ovarian tissue while 74% did not benefit from the surgery. The role of preoperative evaluation of anti-müllerian hormone (AMH) serum level, follicular stimulating hormone (FSH) serum level, and trans-abdominal ultrasound for the antral follicle count to predict the detection of primordial follicles in the harvested ovarian tissue is unclear. Study design, size, duration We conducted a retrospective analysis of all patients ≤ 18 years old who were referred for fertility preservation counseling due to NIPOI at a single tertiary hospital between 2010 and 2020. If initial evaluation suggested a diminished ovarian reserve and at least one positive parameter indicating a follicular activity (AMH > 0.16ng/ml, FSH ≤ 20mIU/ml, detection of ≥ 1 antral follicle by transabdominal sonography), OTCP was offered. Patients with 46XY gonadal dysgenesis were excluded. Participants/materials, setting, methods OTCP was performed laparoscopically in all cases. A fresh sample of cortical tissue was fixed in buffered formaldehyde for histological analysis. The rest of the ovarian tissue was cut into small cuboidal slices 1–2 mm in thickness and cryopreserved. After the serial sections, the histological slides were evaluated for the presence of follicles by a certified pathologist. Follicles were counted and categorized as primordial, primary, and secondary. Main results and the role of chance During the study period, 39 patients with suspected NIPOI were referred to the fertility preservation center. Thirty-seven patients included in the study were diagnosed with Turner’s syndrome (n = 28), Galactosemia (n = 3), Blepharophimosis-Ptosis-Epicanthus Inversus syndrome (n = 1), and idiopathic NIPOI (n = 6). Of 28 patients with Turner’s syndrome, 6 had 45X monosomy, 15 had mosaicism and 7 had structural anomalies in X-chromosome. One patient with gonadal dysgenesis and one with the presence of Y-chromosome in 20% of somatic cells were excluded from the study. OTCP was conducted in 14 patients with at least one positive parameter suggesting ovarian function. No complications of the surgical procedure or the anesthesia were observed. Primordial follicles were found in all patients with two or three positive parameters (100%) and in three of six cases with one positive parameter (50%). In total, of the 14 patients who underwent OTCP with at least one positive parameter, 11 (79%) had primordial follicles at biopsy (mean 23.9, range 2–47). This study demonstrates a positive predictive value of 79% for the detection of primordial follicles in patients who had at least one positive parameter of ovarian reserve evaluation. If two or three parameters were positive, the positive predictive value increased to 100%. Limitations, reasons for caution This study did not examine the negative predictive value of our protocol as OTCP was not recommended in the absence of positive parameters. The future fertility potential of cryopreserved tissue in the population with NIPOI is unclear and should be discovered in further studies. Wider implications of the findings: We suggest the evaluation of ovarian reserve by antral follicles count, AMH, and FSH serum levels prior to OTCP in patients with NIPOI. By recommendation of OTCP only if ≥ 1 parameter suggesting the ovarian function is positive, unnecessary procedures can be avoided. Trial registration number Not applicable

Salpingectomy is the most widely used treatment for hydrosalpinx. The effect of salpingectomy on the stimulation response during subsequent IVF treatment, however, remains unclear. The aim of this systematic review was to evaluate the ovarian response and pregnancy outcome of IVF treatment carried out after salpingectomy compared with other pre-IVF treatment options for hydrosalpinx. We conducted a literature search using PubMed, Ovid MEDLINE, Google Scholar, ClinicalTrials.gov and the Cochrane Central Register of Controlled Trials. Five randomized studies and nine observational studies were included in the systematic review and evaluated using Cochrane Collaboration's tool for randomized, Newcastle–Ottawa scale for observational studies and GRADE guidelines for certainty of evidence assessment. The mean number of retrieved oocytes was similar between the groups in randomized (mean difference [MD] = –0.03, 95% CI –0.75 to 0.70) and observational studies (MD = –0.15, 95% CI –2.32 to 2.02). Live birth (RR 1.59, 95% CI 1.17 to 2.16), clinical pregnancy (RR 1.27, 95% CI 1.02 to 1.57) and implantation rates (RR 1.55, 95% CI 1.16 to 2.08) were higher in the salpingectomy group in randomized studies. The present systematic review and meta-analysis showed that salpingectomy does not impair the ovarian response during subsequent IVF treatment.

Objective To compare the influence of dual suppression with the use of GnRH agonist plus aromatase inhibitor compared with suppression with the use of GnRH agonist alone or no suppression at all in patients with idiopathic recurrent implantation failure (RIF). Design Retrospective cohort study. Setting University-affiliated reproductive center. Patient(s) A total of 523 infertile women who failed two blastocyst transfers underwent a third frozen blastocyst transfer. Women with known endometriosis were excluded. Intervention(s) A total of 204 subjects were not pretreated, 143 received 2 months of GnRH agonist (3.75 mg intramuscular leuprolide acetate monthly) only, and 176 received GnRH agonist and aromatase inhibitor (5 mg oral letrozole daily for 60 days). Demographic and stimulation information was collected and cycle outcomes reported. Main Outcome Measure(s) Clinical pregnancy rates. Result(s) Age, antral follicle count, basal FSH levels, duration of infertility, previous pregnancies, and full-term deliveries were similar (P>.05). Clinical pregnancy rates were higher among women who received GnRH agonist plus letrozole compared with women who received GnRH agonist only or women without pretreatment (63%, 42%, and 40%, respectively; P Conclusion(s) In patients with RIF, treatment with a GnRH agonist plus letrozole may improve live birth rates in subsequent cycles. We hypothesize that this improvement is due to alterations in the endometrium receptivity or treatment of undiagnosed endometriosis.

Study question Do the stage and grade of malignancy affect the fertility preservation outcome in females? Summary answer Patients with high-grade cancer have a decreased number of retrieved mature oocytes and cryopreserved embryos. What is known already Cancer has local and systemic effects on the host. The effects of cancer spread and aggressiveness on the ovarian function and stimulation response remain unclear. Study design, size, duration Retrospective cohort study evaluating data of all fertility preservation treatment cycles among women with cancer at the reproductive unit of the McGill University Health Centre in the period from 2008 to 2017. Participants/materials, setting, methods Study inclusion criteria were age 18-38 years, first stimulation cycle, GnRH-antagonist protocol and early follicular phase stimulation start. Only one stimulation cycle per patient was included. Patients with ovarian pathology, previous ovarian surgery and previous chemo- or radiotherapy were excluded. The outcomes of women with low-stage cancer (local tumor Stage I-II, no lymph node involvement, no metastases) were compared with those with high-stage disease (local tumor Stage III-IV, lymph node involvement or metastases). Similarly we compared those with low-grade (G1-2) and high-grade (G3-4) malignancies. The primary outcome measure was the number of mature oocytes retrieved. The secondary outcomes included the total number of retrieved oocytes, the number of vitrified oocytes, and the number of frozen embryos. We used Student's t-test for normally distributed data and Wilcoxon test for skewed data. To determine factors associated with good fertility preservation outcome defined as over 10 retrieved mature oocytes, we used multivariate logistic regression. Main results and the role of chance A total of 147 patients were included in the final analysis. Age, body mass index, ovarian reserve parameters of the study groups in stage- and grade-based analyses were similar. Compared to women with low-stage cancer (n = 83), those with high-stage cancer (n = 64) required a higher dose of gonadotropin (P = 0.02). The number of retrieved mature oocytes (9 (7-13) versus 8 (5-12); P = 0.37) and vitrified oocytes (10 (7-15) versus 10 (7-13); P = 0.53) were similar between the two groups. However, in cycles where fertilization of all retrieved oocytes was performed, the fertilization rate (82.7% versus 71.5%; P = 0.03) and the number of vitrified embryos (6.2 ± 3.2 versus 4.3 ± 2.1; P = 0.01) were higher in the low-stage group. Compared to patients with low-grade cancer (n = 62), those with high-grade disease (n = 85) had significantly lower number of retrieved mature oocytes (11 (7-15) versus 8 (5-11); P = 0.002) and vitrified oocytes (12 (8-15) versus 10 (7-11); P = 0.005). The number of vitrified embryos was lower in high-grade group (6.5 ± 3.5 versus 4.6 ± 2.3; P = 0.03) in cycles where the fertilization was performed. In multivariate logistical analysis, the low-grade cancer was significantly associated with retrieval of over 10 mature oocytes (OR = 4.26; 95% CI 1.82-9.98; P = 0.0009). Limitations, reasons for caution The main limitations of the study include its retrospective design and the relatively small sample size in the embryological outcome analysis. The results of our study should be viewed with caution as different malignancy types were included in the study groups, although their distribution between the study groups was similar. Wider implications of the findings Cancer grade seems to have a negative impact on the fertility preservation outcome and the ovarian stimulation response. Study funding/competing interest(s) Authors have not received any funding to support this study. There are no conflicts of interest to declare.

Results: The search produced a total of 924 results. After duplicate removal and primary review, 41 articles were selected for full review, and 11 studies that reported the outcome of interest were included in the final meta-analysis. In total, 13871 carriers of BRCA1 and BRCA2 mutations were identified. The pooled prevalence rates of EC and UPSC in BRCA1/2 mutations carriers were 82/13827 (0.59%) and 19/11582 (0.16%), respectively. EC prevalence was 46/7429 (0.62%) in BRCA1, and 17/3546 (0.47%) in BRCA2 mutation carriers, with RR of 1.18 (95% CI 0.7-2.0). For UPSC, the prevalence was 15/7429 (0.2%) and 3/3546 (0.08%) among BRCA1 and BRCA2 mutation carriers, respectively, (RR=1.39, 95% CI 0.5-3.7). Conclusions: This meta-analysis suggests a slightly increased risk of EC in BRCA mutation carriers, mainly for BRCA1. The absolute risk is low and needs to be balanced with the potential mild increase in surgical morbidity associated with the addition of a hysterectomy. Download : Download high-res image (261KB) Download : Download full-size image

Objective Risk-reducing salpingo-oophorectomy (RRSO) is standard treatment among women with BRCA mutations. The aim of this meta-analysis is to evaluate the risk of endometrial cancer (EC) in BRCA1 or BRCA2 germline mutation carriers and to examine the justifiability of prophylactic hysterectomy at the time of RRSO. Data Sources PubMed, Cochrane Central Register of Controlled Trials, BIOSIS, Medline (Ovid), Web of Science, ClinicalTrials.gov, and Google Scholar were searched. Eleven articles were selected and analyzed using the OpenMetaAnalyst 2012 software. Methods of Study Selection Randomized controlled studies, cohort studies, and case-control studies evaluating the risk of EC and specifically uterine papillary serous carcinoma (UPSC) in germline BRCA1/2 mutation carriers were included. Articles were excluded if they did not meet the inclusion criteria, or if data were not reported and the authors did not respond to inquiries. We assessed the methodological quality of the included studies on the basis of the Newcastle-Ottawa scale. Dichotomous results from each of the studies eligible for the meta-analysis were expressed as the proportion of patients with EC or UPSC per total number of BRCA mutation carriers, with 95% confidence interval (CI). The Mantel–Haenszel statistical method was used. Tabulation, Integration, and Results Eleven studies reported the outcome of interest and were included in the final meta-analysis. In total, 13 871 carriers of BRCA1 and BRCA2 mutations were identified. The pooled prevalence rates of EC and UPSC in BRCA1/2 mutation carriers were 82/13 827 (0.59%) and 19/11 582 (0.16%), respectively. The EC prevalence was 46/7429 (0.62%) in BRCA1 mutation carriers and 17/3546 (0.47%) in BRCA2 mutation carriers, with relative risk of 1.18 (95% CI, 0.7–2.0). For UPSC, the prevalence was 15/7429 (0.2%) and 3/3546 (0.08%) among BRCA1 and BRCA2 mutation carriers, respectively, (relative risk 1.39; 95% CI, 0.5–3.7). Conclusion Most studies in this meta-analysis suggest a slightly increased risk of EC in BRCA mutation carriers, mainly for BRCA1. The decision regarding concurrent hysterectomy should be tailored individually to each patient on the basis of the patient's age, type of mutation, future need for hormone replacement treatment, history of breast cancer, tamoxifen use, and personal operative risks.

Over the last 30 years, the caesarean section rate has reached global epidemic proportions. This trend is driven by multiple factors, an important one of which is the use and inconsistent interpretation of the electronic fetal monitoring (EFM) system. Despite its introduction in the 1960s, the EFM has not definitively improved neonatal outcomes, yet it has since significantly contributed to a seven-fold increase in the caesarean section rate. As we attempt to reduce the caesarean rates in the developed world, we should consider focusing on areas that have garnered little attention in the literature, such as physician sensitization to the poor predictive power of the EFM and the research method biases that are involved in studying the abnormal heart rate patterns—umbilical cord pH relationship. Herein, we apply Bayes theorem to different clinical scenarios to illustrate the poor predictive power of the EFM, as well as shed light on the principle of protopathic bias, which affects the classification of research outcomes among studies addressing the effects of the EFM on caesarean rates. We propose and discuss potential solutions to the aforementioned considerations, which include the re-examination of guidelines with which we interpret fetal heart rate patterns and the development of noninvasive technologies that evaluate fetal pH in real time.

Background Prenatal serum screening is an important modality to screen for aneuploidy in pregnancy. The addition of placental growth factor (PLGF) to screen for trisomy 21 remains controversial. Objective To determine whether the addition of PLGF to combined serum aneuploidy screening improves detection rates (DRs) for trisomy 21. Study Design We performed a systematic review of the literature until October 2019 to determine the benefits of adding PLGF to prenatal screening. We performed a goodness-of-fit test and retrieved the coefficient of determinations (R 2) as a function of false positive rates (FPRs), providing mean-weighted improvements in the DRs after accounting for PLGF levels. Results We identified 51 studies, of which 8 met inclusion criteria (834 aneuploidy cases and 105,904 euploid controls). DRs were proportional to FPR across all studies, ranging from 59.0 to 95.3% without PLGF and 61.0 to 96.3% with PLGF (FPR 1–5%). Goodness-of-fit regression analysis revealed a logarithmic distribution of DRs as a function of the FPR, with R 2 = 0.109 (no PLGF) and R 2 = 0.06 (PLGF). Two-sample Kolmogorov–Smirnov's test reveals a p-value of 0.44. Overall, addition of PLGF improves DRs of 3.3% for 1% FPR, 1.7% for 3% FPR, and 1.4% for 5% FPR, respectively. Conclusion Addition of PLGF to prenatal screening using serum analytes mildly improves trisomy 21 DRs as a function of FPRs.

Objective To review short- and long-term complications associated with intraoperative rupture of benign ovarian cysts. Data Sources The Cochrane Central Register of Controlled Trials, BIOSIS, Medline (Ovid), Web of Science, ClinicalTrials.gov, and Google Scholar were searched using the following terms and their combinations: “spillage,” “rupture,” “leakage,” “ovarian cyst,” “teratoma,” “dermoid,” “operative,” “surgery,” “outcome.” Methods of Study Selection Randomized controlled and observational studies evaluating the operative outcomes of surgical treatment of ovarian cysts with intraoperative spillage compared with those of surgical treatment of ovarian cysts without spillage were included. A systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed. Tabulation, Integration, and Results A total of 28 studies were included in the qualitative analysis and 12 in the quantitative analysis. Ovarian cyst diameter was not found to be associated with the risk for spillage (relative risk [RR] 0.75; 95% confidence interval [CI], –0.33 to 1.82). Intraoperative benign ovarian cyst rupture was not associated with adverse short- and long-term outcomes such as reoperation (RR 1.16; 95% CI, 0.39–3.48), infertility (RR 0.73; 95% CI, 0.15–3.63), transient fever (RR 3.22; 95% CI, 0.83–12.51), and readmission (RR 1.00; 95% CI, 0.33–2.98). However, intraoperative spillage was found to be associated with increased risk for benign recurrence (RR 3.1; 95% CI, 1.05–9.14). A subgroup analysis of the studies that included only dermoid cysts showed an association between intraoperative cyst rupture and postoperative chemical peritonitis (RR 9.36; 95% CI, 1.20–73.28). Conclusion Intraoperative ovarian cyst spillage of a benign cyst is associated with limited adverse clinical outcomes. Although the surgical approach (minimally invasive vs open) should not be affected by the concern regarding an intraoperative cyst rupture, maximal efforts should be made to prevent intra-abdominal spillage.

The curvilinear relationship between a screening test’s positive predictive value (PPV) and its target disease prevalence is proportional. In consequence, there is an inflection point of maximum curvature in the screening curve defined as a function of the sensitivity (a) and specificity (b) beyond which the rate of change of a test’s PPV declines sharply relative to disease prevalence (ϕ). Herein, we demonstrate a mathematical model exploring this phenomenon and define the prevalence threshold point (ϕe) where this change occurs as: Understanding where this prevalence point lies in the curve has important implications for the interpretation of test results, the administration of healthcare systems, the implementation of public health measures, and in cases of pandemics like SARS-CoV-2, the functioning of society at large. To illustrate the methods herein described, we provide the example of the screening strategies used in the SARS-CoV-2 (COVID-19) pandemic, and calculate the prevalence threshold statistic of different tests available today. This concept can help contextualize the validity of a screening test in real time, thereby enhancing our understanding of the dynamics of the current pandemic.

Research question: Does newborn gender affect placental histopathology pattern and perinatal outcome in singleton live births following IVF treatment? Design: Retrospective cohort study evaluating data of all live births from one academic tertiary hospital following IVF treatment during 2009–2017. All patients had placentas sent for pathological evaluation irrelevant of maternal and fetal complications status. Exclusion criteria were abnormal uterine cavity findings, previous uterine surgery, in-vitro maturation cycles, gestational carrier cycles, oocyte recipient cycles, preimplantation genetic diagnosis cycles and multiple pregnancies. The primary outcomes included anatomical, inflammation, vascular malperfusion and villous maturation placental features. The secondary outcomes included fetal, maternal, perinatal and delivery complications. A multivariate analysis was conducted to adjust the results for factors potentially associated with placental pathology features. Results: A total of 1057 live births were included in the final analysis and were allocated to the study groups according to fetal gender: males (n = 527) and females (n = 530). After adjustment for potential confounding factors, male gender was significantly associated with villous agglutination (odds ratio [OR] 9.8; 95% confidence interval [CI] 1.4–78.2), avascular villi (OR 4.1; 95% CI 1.3–12.6) and maternal vascular malperfusion (OR 1.8; 95% CI 1.2–2.7). Female gender was significantly associated with bilobed placenta (OR 0.2; 95% CI 0.06–0.8) and subchorionic thrombi (OR 0.5; 95% CI 0.3–0.9). The prevalence of adverse fetal, maternal and delivery outcomes was similar between the groups. Conclusions: Newborn gender has a significant impact on the placental histopathology pattern, which can contribute to the development of adverse perinatal outcomes.

Purpose To evaluate the effect of non-cavity-distorting intramural leiomyomas on the placental histopathology pattern and perinatal outcome in singleton live births resulting from in vitro fertilization treatment. Methods The study population included all singleton live births following in vitro fertilization treatment with autologous oocytes during the period from 2009 to 2017. Primary outcomes included anatomical, inflammation, vascular malperfusion, and villous maturation placental features. Secondary outcomes included fetal, maternal, delivery, and perinatal complications. Results A total of 1119 live births were included in the final analysis and were allocated to the group of pregnancies with non-cavity-distorting intramural myomas (n = 101) and without myomas (n = 1018). After the adjustment for confounding factors, the non-cavity-distorting intramural myomas were found to be significantly associated with assisted placental delivery (OR 2.4; 95% CI 1.5-3.9), furcate cord insertion (OR 3.6; 95% CI 1.4-9.3), circumvallate membranes insertion (OR 5.2; 95% CI 1.4-19.3), chronic deciduitis (OR 8.2; 95% CI 1.6-42.2), focal intramural fibrin deposition (OR 25.1; 95% CI 2.1-306.2), subchorionic thrombi (OR 3.6; 95% CI 1.7-7.6), maternal vasculopathy (OR 2.5; 95% CI 1.2-5.5), and chorangioma (OR 5.9; 95% CI 1.4-25.2) as well as with the failure of labor progress (OR 2.4; 95% CI 1.3-4.4) and induction (OR 3.2; 95% CI 1.2-9.0). Conclusion Intramural non-cavity-distorting myomas have a significant impact on the placental histopathology with a higher incidence of dysfunctional labor.

Study Objective Evaluate the shift in surgical trends for myomectomy and subsequent changes in the number of uterine ruptures over the years. Methods Retrospective analysis utilizing the HCUP-NIS database. Evaluating women, aged 18 – 40 years, who underwent myomectomy by laparoscopy or laparotomy, and who subsequently had uterine rupture between 2005 and 2014. Statistical analysis focused on the odds ratio of having uterine rupture after a myomectomy and the trends over the years. Results Of a total 54,146 myomectomies, there were 237 uterine ruptures, which stands for 0.43%. Mean age was 31.8 years, mainly Caucasians and had private insurance. The procedure was performed mainly by laparotomy with 97.7%, and 2.3% were performed by laparoscopy. There was a decrease of total myomectomies from 6646 in 2005 to 4589 in 2014. The numbers of uterine rupture per 1,000 myomectomies were 4.2 after laparotomy and 10.6 after laparoscopic approach. Conclusion The myomectomy trend changed in recent years with a greater predominance of laparotomies over laparoscopies. Laparoscopic myomectomy may by itself increase the risk for uterine rupture compared to open approach.

The optimal time to perform cryopreserved embryo transfer (CET) after a failed oocyte retrieval-embryo transfer (OR-ET) cycle is unknown. Similar clinical pregnancy rates were recently reported in immediate and delayed CET, performed after failed fresh OR-ET, in cycles with the gonadotrophin-releasing hormone (GnRH) antagonist protocol. This study compared outcomes of CET performed adjacently (

Objective: To evaluate the effect of the COVID-19 pandemic state on early, 1st trimester pregnancies, in light of a link described between war-induced stress and adverse pregnancy outcomes Design: Retrospective cohort study conducted in a University fertility center Materials and Methods: All 1ST trimester viability scans done since the COVID-19 shut down, March13-May 6, 2020 (Study group), and between March 1-May 17, 2019 (pre-pandemic Control), were reviewed Early 1st trimester pregnancy outcomes (Viable pregnancy, Arrested pregnancy including biochemical pregnancy loss and miscarriage, and ectopic pregnancy (EP)) were measured A multivariate analysis was performed to control for significant confounders Power analysis revealed that a sample size of 58 patients per group has a 90% power with a 15% difference in outcomes and α=5% The study group denied symptoms of COVID-19 Results: 113 women were scanned in the study, and 172 in the control periods (5-11 weeks gestational age) The groups had similar demographics, gestational history, fertility diagnosis and treatment characteristics (Table) No significant differences were noted in the rate of recurrent pregnancy loss (RPL) Viable clinical pregnancy rates were not different between the groups (76 1% vs 80 2% in the pandemic and pre-pandemic groups p= 0 41) No significant difference was seen in number of 1st trimester miscarriage (14 2% vs 12 8% p=0 76), biochemical pregnancies (3 5% vs 1 7% p=0 34), or in total miscarriage rate (22 1% vs 16 9% p=0 32), nor in EP rates (0 9% vs 2 3% p=0 36) Mean serum TSH levels were higher in the control but fell in the normal range for both groups Use of donor sperm was higher in the control and may have favored lower miscarriage rates in that group Conclusions: The COVID-19 pandemic environment does not seem to affect early first-trimester miscarriage rates in asymptomatic patients [Formula presented]

Research question Does breast cancer spread and aggressiveness affect fertility-preservation results? Design Retrospective cohort study of women with breast cancer undergoing fertility-preservation treatment. Inclusion criteria: age 18–38 years and use of gonadotrophin releasing hormone antagonist protocol; exclusion criteria: recurrent cancer, previous oncological treatment, previous ovarian surgery and known ovarian pathology. Stimulation cycle outcomes of women with low-stage breast cancer were compared with those with high-stage disease. Patients with low-grade (G1-2) were compared with those with high-grade (G3) malignancies. Primary outcome: total number of mature oocytes; secondary outcomes: oestradiol level and number of follicles wider than 14 mm on the day of trigger, number of retrieved oocytes and cryopreserved embryos. Results The final analysis included 155 patients. Patients with high-grade tumours (n = 80; age 32 years [28–35]) had significantly lower number of mature oocytes compared with patients with low-grade cancer (n = 75; age 32 years [28–35]; seven mature oocytes [4–10] versus 13 mature oocytes [7–17]; P = 0.0002). The number of cryopreserved embryos was also lower in the high-grade group (three [2–5] versus five [3–9]; P = 0.02). Stage-based analysis revealed a similar number of mature oocytes in high-stage (n = 73; age 32 years [28–35]) compared with low-stage group (n = 82; age 33 years [28–35]; eight mature oocytes [4–13] versus nine mature oocytes [7–15]; P = 0.06). Conclusions High-grade breast cancer has a negative effect on total number of mature oocytes and cryopreserved embryos.

Study Objective To evaluate the prevalence of chronic endometritis (CE) among fertile and infertile women who underwent hysteroscopic polypectomy. Design A retrospective cohort study. Setting University-affiliated tertiary hospital. Patients A total of 277 women who underwent hysteroscopic polypectomy in the period from 2015 to 2018. Interventions Endometrial polyp samples were obtained after hysteroscopy for histopathologic analysis using hematoxylin-eosin and immunohistochemistry staining with CD138 antibodies for plasma cell detection. All infertile women diagnosed with CE were treated with oral doxycycline 100 mg twice daily for 14 days before infertility treatment. Measurements and Main Results The prevalence of CE in infertile women (n = 137) was significantly higher than in those with no history of infertility (n = 140) (22.6% vs 8.6%; p = .001). The prevalence of CE between women with primary infertility and those with secondary infertility was similar (25.0% vs 19.3%; p = .43). Clinical pregnancy (32.3% vs 41.5%; p = .35), live birth (29.0% vs 38.7%; p = .33), and miscarriage (10.0% vs 6.8%; p = .73) rates were similar between infertile women with treated CE and those without CE. A multivariate model showed that diagnosis of infertility was significantly associated with the diagnosis of CE (odds ratio, 3.16; 95% confidence interval, 1.53–6.49). Conclusion In women with endometrial polyps, the prevalence of CE in infertile women is higher than that in fertile women. Pregnancy outcome in infertile women with treated CE was similar to those who were infertile and without CE.

Research question Does the addition of a gonadotrophin-releasing hormone (GnRH) antagonist to cabergoline treatment during the luteal phase in fresh IVF cycles triggered with a GnRH agonist, and planned for freeze-all, reduce the rate of mild and moderate ovarian hyperstimulation syndrome (OHSS)? Design Retrospective cohort study of 480 IVF patients at risk for OHSS with GnRH agonist trigger from 2011 to 2018, stratified into three groups based on treatment received: GnRH agonist trigger alone (Group 1, n = 208), GnRH agonist trigger + cabergoline (Group 2, n = 167) or GnRH agonist trigger + cabergoline + GnRH antagonist (Group 3, n = 105). Data on patient demographics, incidence, severity and symptomatology of OHSS and laboratory findings were collected. Results Group 1 had more free peritoneal fluid than Group 2 (28% versus 19%, P = 0.04) or Group 3 (28% versus 5%, P = 0.001). Group 1 reported abdominal discomfort and bloating more than Group 2 (33% versus 21%, P = 0.01) or Group 3 (33% versus 18%, P = 0.006). Group 1 had more electrolyte abnormalities than Group 2, who had more than Group 3. No patients developed severe OHSS. Mild and moderate OHSS rate was higher in Group 1 (38%) than Group 2 (29%, P = 0.048) or Group 3 (18%, P = 0.006) and in Group 2 than Group 3 (P = 0.046). Conclusion Addition of cabergoline to GnRH agonist triggering in high-risk OHSS patients, and subsequent addition of GnRH antagonist for 5 days in the luteal phase, sequentially reduces the risk of mild and moderate OHSS and improves patient comfort compared with GnRH agonist trigger alone.

Objective To evaluate the impact of lymphoma aggressiveness on ovarian response during fertility preservation treatment. Design Retrospective cohort study. Setting University-affiliated tertiary hospital. Patient(s) Women with lymphoma who underwent ovarian stimulation for fertility preservation in the period from 2009 to 2018. Intervention(s) None. Main Outcome Measure(s) Primary outcome: the number of mature oocytes; secondary outcomes: the number of retrieved oocytes, estradiol level, and number of follicles >14 mm on the day of oocyte maturation trigger. Result(s) Patients with stage I–II lymphoid neoplasms (localized disease) were compared with those with stage III–IV lymphomas (advanced disease). Women with favorable levels of biochemical prognostic markers were also compared with those with unfavorable levels. Women with favorable levels of biochemical prognostic markers (n = 74) had a higher number of mature oocytes compared with patients with unfavorable serum levels (n = 67): 11 (7.8–16) versus 9 (5–11), respectively. The number of mature oocytes was similar between patients with localized (n = 75) and advanced (n = 66) lymphomas. Women with unfavorable combination of stage and biochemical factors had lower number of mature oocytes compared to patients with favorable combination: 8 (5–10) versus 11 (7–16), respectively. Multivariate logistic regression showed that favorable levels of biochemical markers as well as a combination of extent and biochemical parameters were statistically significantly associated with the result of over 10 mature oocytes. Conclusion(s) Highly-aggressive lymphoid neoplasms have a negative impact on ovarian function and response during fertility preservation treatment.

To assess the added value of maturing immature oocytes collected during fertility preservation treatments in women with malignancy. A retrospective case-control study analyzing the results of 327 cancer patients undergoing fertility preservation treatments. Oocyte maturation rates and cycle parameters were compared between 3 types of fertility preservation treatments: (1) stimulated IVF cycle (n = 143), (2) non-stimulated IVM cycle (n = 158), (3) follicle aspiration and oocyte collection from ovarian tissue prepared for ovarian tissue cryopreservation followed by in vitro maturation of the immature oocytes (n = 48). The primary outcome measure was the maturation rate and the number of mature oocytes. The secondary outcomes were oocyte fertilization and embryo development rates. The mean maturation rate in IVF cycles was 38% and in the non-stimulated IVM cycles was 55%. In women who chose to cryopreserve their embryos, similar fertilization and embryo cleavage rates were found in oocytes that matured after stimulated IVF cycles compared to non-stimulated IVM cycles. Gonadotropin-releasing hormone agonist triggering, treatment with aromatase inhibitor, or oral contraceptives use before the cycle did not affect the maturation rate. Ovarian stimulation yields the highest number of oocytes or embryos for cryopreservation. Although the maturation rate of immature oocytes collected in stimulated IVF cycles is low, it is still a viable source of oocytes that can be used to improve the efficacy of fertility preservation treatments by increasing the number of mature oocytes available for freezing or fertilization.

Improved sperm indices have been reported when semen produced on oocyte pick-up (OPU) day is collected with a condom compared with by masturbation among both patients with normozoospermia and those with sperm deficiencies [1, 2]. However, potential benefits of sperm collection by condom have not been evaluated in an in vitro fertilization (IVF) setting. The present study retrospectively investigated the effect of the sperm collection by condom or masturbation on the outcome of OPU-embryo transfer (OPU-ET) cycles. Pregnancy and fertilization rates were compared based on the type of oocyte insemination (IVF-insemination or intracytoplasmic sperm injection), and across sperm deficiencies. This article is protected by copyright. All rights reserved.