Fertility preservation parameters in patients with haematologic malignancy: a systematic review and meta-analysis.

Patients with haematologic malignancies represent one of the most common groups referred for fertility preservation before gonadotoxic oncological treatment. The aim of this systematic review and meta-analysis was to evaluate the effect of haematologic cancer on ovarian reserve and response to ovarian stimulation compared with healthy controls. A total of eight observative studies were included in the final quantitative analysis. Despite a younger age (mean difference -4.17, 95% CI -6.20 to -2.14; P < 0.0001), patients with haematologic malignancy had lower serum anti-Müllerian hormone levels compared with the control group (MD -1.04, 95% CI -1.80 to -0.29; P = 0.007). The marginally higher total recombinant FSH dose (MD 632.32, 95% CI -187.60 to 1452.24; P = 0.13) and significantly lower peak oestradiol serum level (MD -994.05, 95% CI -1962.09 to -26.02; P = 0.04) were demonstrated in the study group compared with the healthy controls. A similar number of retrieved oocytes were achieved in both groups (MD 0.20, 95% CI -0.80 to 1.20; P = 0.69). In conclusion, haematologic malignancies may detrimentally affect ovarian function manifesting in decreased AMH serum levels despite a younger age compared with healthy controls. This effect can be overcome by the application of relevant IVF protocols and stimulation doses to achieve an adequate oocyte yield.

Proteomic signature for detection of high-grade ovarian cancer in germline BRCA mutation carriers.

No current screening methods for high-grade ovarian cancer (HGOC) guarantee effective early detection for high-risk women such as germline BRCA mutation carriers. Therefore, the standard-of-care remains risk-reducing salpingo-oophorectomy (RRSO) around age 40. Proximal liquid biopsy is a promising source of biomarkers, but sensitivity has not yet qualified for clinical implementation. We aimed to develop a proteomic assay based on proximal liquid biopsy, as a decision support tool for monitoring high-risk population. Ninety Israeli BRCA1 or BRCA2 mutation carriers were included in the training set (17 HGOC patients and 73 asymptomatic women), (BEDOCA trial; ClinicalTrials.gov Identifier: NCT03150121). The proteome of the microvesicle fraction of the samples was profiled by mass spectrometry and a classifier was developed using logistic regression. An independent cohort of 98 BRCA mutation carriers was used for validation. Safety information was collected for all women who opted for uterine lavage in a clinic setting. We present a 7-protein diagnostic signature, with AUC >0.97 and a negative predictive value (NPV) of 100% for detecting HGOC. The AUC of the biomarker in the independent validation set was >0.94 and the NPV >99%. The sampling procedure was clinically acceptable, with favorable pain scores and safety. We conclude that the acquisition of Müllerian tract proximal liquid biopsies in women at high-risk for HGOC and the application of the BRCA-specific diagnostic assay demonstrates high sensitivity, specificity, technical feasibility and safety. Similar classifier for an average-risk population is warranted.

Does embryo quality at transfer affect obstetric outcomes and placental findings?

STUDY QUESTION: Do obstetric outcomes and placental findings in pregnancies conceived with IVF vary according to embryo quality? SUMMARY ANSWER: Pregnancies following the transfer of lower-quality embryos were associated with a higher rate of low-lying placentas and several adverse placental lesions. WHAT IS KNOWN ALREADY: A few studies have shown reduced pregnancy and live births rates with poor-quality embryo transfer, yet with comparable obstetric outcomes. None of these studies included placental analysis. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study of 641 deliveries of IVF attained pregnancies between 2009 and 2017 was carried out. PARTICIPANTS/MATERIALS, SETTING, METHODS: Live singleton births after IVF with a single blastocyst transfer at a university-affiliated tertiary hospital were included. Excluded were cycles of oocyte recipients and IVM. We compared pregnancies following the transfer of a poor-quality blastocyst (poor-quality group) or a good-quality blastocyst (controls, good-quality group). During the study period, all placentas from complicated and uncomplicated pregnancies were sent to pathology. Primary outcomes were placental findings, including anatomic, inflammatory, vascular malperfusion, and villous maturation lesions, categorized according to the Amsterdam Placental Workshop Group Consensus. Secondary outcomes included obstetric and perinatal outcomes, adjusted for diminished ovarian reserve, fresh versus frozen transfer, and neonatal gender (as indicated by univariable analysis). MAIN RESULTS AND THE ROLE OF CHANCE: A total of 132 deliveries in the poor-quality group were compared to 509 controls. A diagnosis of diminished ovarian reserve was more common in the poor-quality group than in the control group (14.3% versus 5.5%, respectively, P < 0.001) and more pregnancies in the poor-quality group were following frozen embryo transfer. After adjustment for confounders, poor-quality embryos were associated with a higher rate of low-lying placentas [adjusted odds ratio (aOR) 2.35, 95% CI 1.02-5.41, P = 0.04] and placentas with a higher rate of villitis of unknown etiology (aOR 2.97, 95% CI 1.17-6.66, P = 0.02), distal villous hypoplasia (aOR 3.78, 95% CI 1.20-11.38, P = 0.02), intervillous thrombosis (aOR 2.41, 95% CI 1.39-4.16, P = 0.001), multiple maternal malperfusion lesions (aOR 1.59, 95% CI 1.06-2.37, P = 0.02), and parenchymal calcifications (aOR 2.19, 95% CI 1.07-4.46, P = 0.03). LIMITATIONS, REASONS FOR CAUTION: The study is limited by its retrospective design and the utilization of two grading systems during the study period. In addition, the sample size was limited to detect differences in outcomes of rarer occurrences. WIDER IMPLICATIONS OF THE FINDINGS: The placental lesions demonstrated in our study imply an altered immunological response to the implantation of poor-quality embryos. Yet, these findings were not associated with additional adverse obstetric outcomes and merit reaffirmation in a larger cohort. Overall, the clinical findings of our study are reassuring to clinicians and patients for whom the transfer of a poor-quality embryo is necessary. STUDY FUNDING/COMPETING INTEREST(S): No external funding was obtained for this study. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

The effect of oestrogen dose and duration in programmed frozen cycles on obstetric outcomes and placental findings.

RESEARCH QUESTION: Does programmed frozen embryo transfer (FET) with high-dose oestrogen affect obstetric outcomes and placental findings? DESIGN: A retrospective cohort of live singleton deliveries at a single institution between 2009 and 2017, including deliveries attained by IVF with programmed FET; oocyte recipients were excluded. High-dose oestrogen was defined as a daily dose >6 mg throughout treatment. All placentas were evaluated regardless of complication status and the Amsterdam classification was used to analyse findings. RESULTS: A total of 57 deliveries in the high-dose oestrogen group were compared with 274 controls. The high-dose oestrogen group displayed significantly longer duration of oestrogen treatment (18.8 ± 4.9 versus 13.3 ± 2.7 days, P < 0.001), total cumulative oestrogen dose (149.7 ± 46.1 versus 80.3 ± 16.8 mg, P < 0.001) and lower endometrial thickness (8.5 ± 1.4 versus 9.8 ± 1.7 mm, P < 0.001). After adjustment for confounders, higher dose oestrogen was found to be associated with a lower average birthweight (coefficient -252.4 g, 95% confidence interval [CI] -483.5 to -21.2), a higher rate of low-birthweight neonates (adjusted odds ratio [aOR] 4.88, 95% CI 1.05 to 22.57), bilobated placentas (aOR 3.36, 95% CI 1.04 to 10.89), accessory lobes (aOR 8.74, 95% CI 1.24 to 61.5), accelerated villous maturation (aOR 2.06, 95% CI 1.09 to 3.87), retroplacental haematoma (aOR 5.39, 95% CI 1.11 to 26.13) and maternal malperfusion lesions (aOR 1.46, 95% CI 1.04 to 2.05). CONCLUSION: A higher daily oestrogen dose in programmed FET is associated with low birthweight and placental changes, although this may relate to altered endometrial properties and not to the treatment itself.

Evaluation of ovarian reserve in young females with non-iatrogenic ovarian insufficiency to establish criteria for ovarian tissue cryopreservation.

RESEARCH QUESTION: Can ovarian reserve parameters predict the outcome of ovarian tissue cryopreservation (OTCP) in patients ≤18 years with non-iatrogenic premature ovarian insufficiency (POI)? DESIGN: Retrospective cohort analysis carried out in a single tertiary hospital between August 2010 and January 2020. Thirty-seven patients ≤18 years with non-iatrogenic POI (27 with Turner syndrome, six with POI of unknown aetiology, three with galactosemia and one with blepharophimosis, ptosis, epicanthus inversus syndrome) were included. Three parameters were used to evaluate ovarian reserve: anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH) and transabdominal antral follicle count. Fertility preservation (most commonly OTCP) was offered if ovarian reserve was diminished and one or more parameters was positive. Follicles were counted in ovarian samples obtained at the time of OTCP. RESULTS: Ovarian reserve was diminished in 34 patients and 19 of them had one or more positive parameter. Fourteen (11 aged ≥12 years and 3 aged <12) underwent OTCP, one (14 years old) underwent ovarian stimulation and oocyte cryopreservation and four declined fertility preservation. Follicles were detected in 11 of 14 patients who underwent OTCP with one or more positive parameters (79%), and in all those (100%) who had two or three positive parameters. The median number of follicles was 27 (range 5-64) and 48 (range 21-75) in patients ≥12 years and those <12 years, respectively. CONCLUSION: This study shows that if OTCP is performed in patients with one or more positive parameters of ovarian activity, a 79% positive predictive value is achieved for the detection of follicles. The incorporation of this criterion for OTCP will minimize the risk of harvesting ovarian tissue with a low number of follicles.

Robotic-assisted versus conventional laparoscopic approach in patients with large rectal endometriotic nodule: the evaluation of safety and complications.

AIM: The aim was to compare postoperative complications in patients undergoing the excision of a rectal endometriotic nodule over 3 cm by a robotic-assisted versus a conventional laparoscopic approach. METHODS: We conducted a retrospective cohort study evaluating prospectively collected data. The main interventions included rectal shaving, disc excision or colorectal resection. All the surgeries were performed in one endometriosis reference institute. To evaluate factors significantly associated with the risk of anastomosis leakage or fistula and bladder atony, we conducted a multivariate logistic regression model. RESULTS: A total of 548 patients with rectal endometriotic nodule over 3 cm in diameter (#ENZIAN C3) were included in the final analysis. The demography and clinical characteristics of women managed by the robotic-assisted (n = 97) approach were similar to those of patients who underwent conventional laparoscopy (n = 451). The multivariate logistic regression demonstrated that the surgical approach (robotic-assisted vs. laparoscopic) was not associated with the rate of anastomosis leakage or fistula (adjusted odds ratio [aOR] 1.2, 95% confidence interval [CI] 0.3-4.0) and bladder dysfunction (aOR 0.5, 95% CI 0.1-1.8). A rectal nodule located lower than 6 cm from the anal verge was significantly associated with anastomosis leakage (aOR 4.1, 95% CI 1.4-10.8) and bladder atony (aOR 4.3, 95% CI 1.5-12.3). Anastomosis leakage was also associated with smoking (aOR 3.2, 95% CI 1.4-7.4), significant vaginal infiltration (aOR 2.7, 95% CI 1.2-6.7) and excision of nodules involving sacral roots (aOR 5.6, 95% CI 1.7-15.5). CONCLUSION: The robotic-assisted approach was not associated with increased risk of main postoperative complications compared to conventional laparoscopy for the treatment of large rectal endometriotic nodules.

MYO10 promotes transzonal projection-dependent germ line-somatic contact during mammalian folliculogenesis†.

Granulosa cells of growing ovarian follicles elaborate filopodia-like structures termed transzonal projections (TZPs) that supply the enclosed oocyte with factors essential for its development. Little is known, however, of the mechanisms underlying the generation of TZPs. We show in mouse and human that filopodia, defined by an actin backbone, emerge from granulosa cells in early stage primary follicles and that actin-rich TZPs become detectable as soon as a space corresponding to the zona pellucida appears. mRNA encoding Myosin10 (MYO10), a motor protein that accumulates at the base and tips of filopodia and has been implicated in their initiation and elongation, is present in granulosa cells and oocytes of growing follicles. MYO10 protein accumulates in foci located mainly between the oocyte and innermost layer of granulosa cells, where it colocalizes with actin. In both mouse and human, the number of MYO10 foci increases as oocytes grow, corresponding to the increase in the number of actin-TZPs. RNAi-mediated depletion of MYO10 in cultured mouse granulosa cell-oocyte complexes is associated with a 52% reduction in the number of MYO10 foci and a 28% reduction in the number of actin-TZPs. Moreover, incubation of cumulus-oocyte complexes in the presence of epidermal growth factor, which triggers a 93% reduction in the number of actin-TZPs, is associated with a 55% reduction in the number of MYO10 foci. These results suggest that granulosa cells possess an ability to elaborate filopodia, which when directed toward the oocyte become actin-TZPs, and that MYO10 increases the efficiency of formation or maintenance of actin-TZPs.

Pregnancy complications and placental histology following embryo transfer with a thinner endometrium.

STUDY QUESTION: Are deliveries following IVF with a thinner endometrium associated with adverse perinatal outcomes and placental findings? SUMMARY ANSWER: Live births following IVF with a thinner endometrium are associated with an increased rate of placental-mediated obstetric complications and lower birthweight, while the placentas are notable for gross anatomical and histological malperfusion lesions. WHAT IS KNOWN ALREADY: Past studies have noted a higher rate of adverse outcomes on deliveries following IVF with a thinner endometrium, mainly placental-associated complications. However, no study to date has investigated placental histopathology in such cases. STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study of 1057 deliveries following IVF, between 2009 and 2017. All placentas were sent to pathology irrelevant of pregnancy complication status, per protocol at our institution. PARTICIPANTS/MATERIALS, SETTING, METHODS: Live singleton births from a tertiary university hospital after IVF were compared between patients for whom embryo transfer was performed with an endometrium <9 mm (thinner endometrium group) and patients with an endometrium ≥9 mm (control group). Placental pathologic findings were categorized according to the Amsterdam Placental Workshop Group Consensus. Outcomes were placental findings, including anatomic, inflammatory, vascular malperfusion and villous maturation lesions, as well as obstetric and perinatal outcomes. Continuous and categorical variables were compared as appropriate, and multivariate regression and linear analyses were employed to control for confounders. MAIN RESULTS AND THE ROLE OF CHANCE: A total 292 cases in the thinner endometrium group, and 765 in the control group were compared. Maternal demographics were non-significant between the groups, except for main fertility indication was more commonly diminished reserve in patients with a thinner endometrium and less commonly male factor, P = 0.003. Higher rates of fresh transfers were noted in the control group, while the thinner endometrium group was notable for higher rates of blastocyte transfers. After adjustment for confounders, deliveries in the thinner endometrium group were associated with an overall higher rate of main placental-mediated complications, 22.9% versus 15.2%, P = 0.003, and significantly lower birthweight, ß -100.76 g (-184.4-(-17.0)). Placentas in the thinner endometrium group were notable for reduced thickness and a higher rate of bilobated placentas. Placental histology in the thinner endometrium group demonstrated a higher rate of maternal malperfusion lesions. LIMITATIONS, REASONS FOR CAUTION: The study was limited by its retrospective design and lack of data regarding prior uterine surgery. In addition, sample size was limited for detection of differences in outcomes of rarer occurrence and for analysis as per a stricter definition of thin endometrium. WIDER IMPLICATIONS OF THE FINDINGS: Excess obstetric risks should be taken into consideration while planning an embryo transfer with a thinner endometrium. Further studies are needed to assess the yield of cycle cancellation and the effect of potential preventive measures such as Micropirin treatment. STUDY FUNDING/COMPETING INTEREST(S): No funding was used and the authors report no conflicting interests. TRIAL REGISTRATION NUMBER: N/A.

The effect of endometriosis on placental histopathology and perinatal outcome in singleton live births resulting from IVF.

RESEARCH QUESTION: Does endometriosis have an effect on the placental histopathology pattern and perinatal outcome in singleton live births resulting from IVF treatment? DESIGN: Retrospective cohort study evaluating the data on all live births following IVF treatment between 2009 and 2017 at one university-affiliated tertiary hospital. All patients had placentas sent for full gross and histopathology assessment, irrespective of complication status or delivery mode. The primary outcomes of the study included anatomical, inflammation, vascular malperfusion and villous maturation placental disorders. The secondary outcomes included fetal, maternal, perinatal and delivery complications. A multivariate logistic model was used to adjust the results for confounding factors potentially associated with significant placental characteristics. RESULTS: A total of 1057 live births were included in the final analysis and were allocated to the group of women with endometriosis (n = 75) and those without (n = 982). After adjustment for confounding factors, endometriosis was found to be significantly associated with acute chorioamnionitis with moderate to severe maternal (odds ratio [OR] 2.2, 95% confidence interval [95% CI] 1.1-4.6) and fetal (OR 4.9, 95% CI 1.8-13.1) inflammatory response, placenta previa (OR 3.1, 95% CI 1.2-7.8), subchorionic fibrin deposition (OR 3.4, 95% CI 1.2-9.1), intervillous thrombosis (OR 3.4, 95% CI 1.5-8.1), and fetal vascular malperfusion (OR 5.1, 95% CI 1.4-18.1), as well as with preterm birth (OR 2.5, 95% CI 1.4-4.7). CONCLUSIONS: Endometriosis has a significant impact on the placental histopathology and is associated with a higher incidence of preterm birth.

Placental histology and pregnancy complications following intracytoplasmic sperm injection for non-male factor infertility.

PURPOSE: To assess obstetric outcomes and placental histology following intracytoplasmic sperm injection (ICSI), for non-male infertility. METHODS: This was a retrospective cohort of live born singleton deliveries after in vitro fertilization (IVF) at a single university affiliated medical center between 2009 and 2017. Excluded were IVF cycles with male infertility and oocyte recipients. We compared obstetric outcomes and placental histology in cases ICSI was performed (ICSI group) and cases with no ICSI (IVF group). RESULTS: A total of 400 deliveries following ICSI were compared to 218 in the IVF group. Maternal age was similar between the groups, while diminished ovarian reserve was more common among ICSI patients and tubal disease less common (p < 0.001). The rate of blastocyte transfer was also significantly lower in the ICSI group-67.5% vs. 77%, p = 0.01. Pregnancies following ICSI were characterized by similar rates of preeclampsia, preterm birth, and small for gestational age neonates. Although cesarean delivery rate was significantly higher in the group, this did no attain significance after adjustment for confounders. Placentas in the ICSI group were notable for a lower rate of villitis of unknown etiology (1% vs. 4.5%, p = 0.007) and a higher rate of maternal surface calcifications (33% vs. 23.8%, p = 0.01) after adjustment for confounders. CONCLUSION: The employment of ICSI with no male indication is associated with similar obstetric outcomes. Despite isolated placental differences among many investigated, placental histology seems overall comparable as well. These results are reassuring to clinicians and patients.

Does a history of recurrent pregnancy loss affect subsequent obstetric outcomes and placental findings in in vitro fertilization?

PURPOSE: To assess perinatal outcomes and placental findings in in vitro fertilization (IVF) patients with previous recurrent pregnancy loss (RPL). METHODS: This was a retrospective cohort of live singleton births following IVF at a single university-affiliated center between 2009 and 2017. Outcomes were compared between patients with previous RPL, defined as two miscarriages (RPL group), and patients without RPL (control group). Placental examination was performed for all deliveries irrelevant of complications, and findings categorized according to the Amsterdam Placental Workshop Consensus. RESULTS: One hundred seventy-two deliveries of women with previous RPL (RPL group) were compared to 885 controls. Maternal age, 36.2 ± 4.2 vs. 35.4 ± 4.2 years, p = 0.02, and rate of uterine fibroids, 12.7% vs. 7.3%, p = 0.01, were higher in the RPL group. The rate of nulliparity was lower in the RPL group, 63.3% vs. 74.1%, p = 0.003. Unexplained infertility and diminished ovarian reserve were more common in the RPL group and male factor infertility in controls. There was a lower rate of fresh embryo transfer in the RPL group, 50.5% vs. 64.7%, p < 0.001, and reduced endometrial thickness. Similar obstetric outcomes were noted in the groups after adjustment for confounders. Placental examinations were notable for lower placental thickness, ß - 0.17 cm, 95%CI - 0.30-(- 0.0), a lower rate of velamentous cord insertion, aOR 0.44, 95%CI 0.20-0.95, and a higher rate of villous infarction, aOR 2.82, 95%CI 1.28-6.20 in the RPL group. CONCLUSION: In IVF patients with a history of RPL, subsequent deliveries were associated with a limited number of placental lesions, yet with similar obstetric outcomes.

Placental histology following assisted hatching in fresh transfer cycles.

PURPOSE: To assess placental histological findings following assisted hatching in fresh transfer in vitro fertilization cycles. METHODS: Evaluation of a historic cohort of live singleton deliveries after fresh embryo transfer (ET) at a single university medical center between 2009 and 2017. We compared perinatal outcomes and placental histology in cases where assisted hatching was performed prior to ET (AH group) and cases with no AH (no AH group). RESULTS: Overall, 166 deliveries following AH were compared to 494 deliveries with no AH. Patients' demographics were similar between the groups. Median antral follicle count was significantly lower in the AH group, median 11 (range 1-50) vs. 16 (range 1-80), p < 0.001, and the primary indication for infertility treatment significantly more often diminished ovarian reserve (p < 0.001). Cycle characteristics in the AH group included a higher gonadotropin dose employed, and a lower rate of single and blastocyte transfer. Pregnancies following AH were associated with less low-lying placentas, 0.6% vs. 6.2%, p = 0.001, and comparable for other perinatal outcomes. After adjusting for confounders, the rate of bilobated placentas was higher following AH, aOR 7.10, 95% CI 1.50-33.51. The rate of perivillous depositions was higher with AH, aOR, 95% CI 3.18, 1.46-6.93, and the rate of chorangiosis lower in this group, aOR, 95% CI 0.32, 0.11-0.93. The overall rate of vascular lesions was similar between the groups. CONCLUSION: Pregnancies following AH are notable for a lower rate of placenta previa, yet a higher rate of bilobated placentas and perivillous depositions and less chorangiosis, warranting further investigation.

Endometrial Cancer in Germline BRCA Mutation Carriers: A Systematic Review and Meta-analysis.

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.

Short- and Long-Term Complications of Intraoperative Benign Ovarian Cyst Spillage: A Systematic Review and Meta-analysis.

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 Montreal Criteria and uterine transplants in transgender women.

Ever since its first documented live birth in 2014, the use of uterine transplantation (UTx) for the treatment of absolute uterine factor infertility (UFI) has seen major clinical advances, which include the use of alternative surgical approaches, different donor states, and diverse patient populations. In addition to the thorough research programs that developed the technique, this accomplishment has occurred in large part following a number of ethical frameworks, such as the Montreal Criteria and the Indianapolis Consensus, which paved the way to transition from experimental animal trials to human ones. To date, over 60 uterine transplants have been performed in the world, and at least 18 births have been thus far confirmed. While the procedure remains experimental, the vast knowledge and procedural experience amassed over the last 20 years of rigorous research have hinted at the next step of discovery. In particular, advancing social circumstances have prompted the question regarding the use of this technology in transgender individuals. Though the potential use of uterine transplants in the transgender population has been hypothesized, no in-depth ethical framework has been developed towards this purpose. Herein, we explore the ethical issues revolving around the use of this technology in this patient population and provide key insights that may advance this cause.

Transvaginal Sonography Post-Office Hysteroscopy as a Screening Tool for Tubal Patency: A Reliable and Feasible Technique in an Outpatient Setting.

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.

COVID-19 pandemic effect on early pregnancy: are miscarriage rates altered, in asymptomatic women?

PURPOSE: To evaluate the effect of the COVID-19 pandemic state on early, first-trimester pregnancies. METHODS: A retrospective cohort study conducted at a university-affiliated fertility center in Montreal, Quebec, since the COVID-19 shut down, March 13 until May 6, 2020. Included: all women who came for a first-trimester viability scan during the study period (Study group) and between March 1, 2019 and May 17, 2019, approximately one year prior (Control). The study population denied symptoms of COVID-19. We reviewed all first trimester scans. Early first-trimester pregnancy outcomes (Viable pregnancy, arrested pregnancy including biochemical pregnancy loss and miscarriage, and ectopic pregnancy) were measured as total number and percentage. A multivariate analysis was performed to control for other potentially significant variables, as was a power analysis supporting sample size. RESULTS: 113 women came for a first-trimester viability scan in the study period, and 172 in the control period (5-11 weeks gestational age), mean maternal age 36.5 ± 4.5 and 37.2 ± 5.4 years (p = 0.28). Viable clinical pregnancy rate was not different between the two groups (76.1 vs. 80.2% in the pandemic and pre-pandemic groups p = 0.41). No significant difference was seen in the total number of arrested pregnancies (defined as the sum of biochemical, 1st trimester miscarriages, and blighted ova) (22.1 vs. 16.9% p = 0.32), or in each type of miscarriage. CONCLUSION: The COVID-19 pandemic environment does not seem to affect early first-trimester miscarriage rates in asymptomatic patients.

An age-based sperm nomogram: the McGill reference guide.

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 < 0.001) on all parameters (except morphology) which demonstrated a biphasic trend peaking in the fourth decade of life. In the ARL group, age had a significant influence (P < 0.01) on all semen parameters except sperm concentration and morphology. However, unlike in the entire dataset, only semen volume demonstrated a biphasic trend in the ARL group (peaking in the fourth decade of life), whereas other parameters either remained unchanged (concentration and morphology) or consistently declined with age (sperm motility, progressive motility and total sperm count). Percentile-based nomograms were generated for individuals between the ages of 20 and 60 years in the entire dataset and in the ARL group. 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.

Trends in ovarian hyperstimulation syndrome hospitalization rates in the USA: an ongoing concern.

Ovarian hyperstimulation syndrome (OHSS) is a serious, almost exclusively, iatrogenic complication of ovarian stimulation. Many techniques have been developed over the past 25 years to decrease OHSS risks, and most have been in common use for 15-20 years. In view of these techniques, it could be hypothesized that severe OHSS rates would decrease or almost disappear. According to the US National ART Surveillance System, rates did not change significantly between 2000 and 2009, at 106 OHSS cases per 10,000 IVF cycles annually. In the present study, OHSS-related hospital admissions were evaluated to establish whether a decline has occurred in OHSS admissions since the development of preventative strategies. A retrospective-population-based study was conducted using data from the Health-Care Cost and Utilization Project-Nationwide-Inpatient-Sample database between 2004 and 2014 inclusively. Between 2004 and 2008, admissions of OHSS decreased in absolute numbers and rates; however, these statistics plateaued, remaining stable between 2008 and 2014. Despite this, OHSS remains a concern and is clearly not a disease of the past. The financial burden of OHSS hospitalizations likely persists. Although techniques have resulted in a decrease in OHSS admissions since 2004, this change has plateaued, and therefore efforts to further reduce OHSS must continue.

Influence of stage and grade of breast cancer on fertility preservation outcome in reproductive-aged women.

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.