Guideline No. 446: Hysteroscopic Surgery in Fertility Therapy.

OBJECTIVE: To evaluate the indications, benefits, and risks of hysteroscopy in the management of patients with infertility and provide guidance to gynaecologists who manage common conditions in these patients. TARGET POPULATION: Patients with infertility (inability to conceive after 12 months of unprotected intercourse) undergoing investigation and treatment. BENEFITS, HARMS, AND COSTS: Hysteroscopic surgery can be used to diagnose the etiology of infertility and improve fertility treatment outcomes. All surgery has risks and associated complications. Hysteroscopic surgery may not always improve fertility outcomes. All procedures have costs, which are borne either by the patient or their health insurance provider. EVIDENCE: We searched English-language articles from January 2010 to May 2021 in PubMed/MEDLINE, Embase, Science Direct, Scopus, and Cochrane Library (see Appendix B for MeSH search terms). VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional recommendations). INTENDED AUDIENCE: Gynaecologists who manage common conditions in patients with infertility. TWEETABLE ABSTRACT: When offering hysteroscopic surgery to patients with infertility, ensure it improves the live birth rate. SUMMARY STATEMENTS: RECOMMENDATIONS.

Guideline No. 435: Minimally Invasive Surgery in Fertility Therapy.

OBJECTIVE: To evaluate the benefits and risks of minimally invasive procedures in the management of patients with infertility and provide guidance to gynaecologists who manage common conditions in these patients. TARGET POPULATION: Patients with infertility (inability to conceive after 12 months of unprotected intercourse) undergoing investigation and treatment. BENEFITS, HARMS, AND COSTS: Minimally invasive reproductive surgery can be used to treat infertility, improve fertility treatment outcomes, or preserve fertility. All surgery has risks and associated complications. Reproductive surgery may not improve fertility outcomes and may, in some instances, damage ovarian reserve. All procedures have costs, which are borne either by the patient or their health insurance provider. EVIDENCE: We searched English-language articles from January 2010 to May 2021 in PubMed/MEDLINE, Embase, Science Direct, Scopus, and Cochrane Library (see Appendix A for MeSH search terms). VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix B (Tables B1 for definitions and B2 for interpretations of strong and conditional [weak] recommendations). INTENDED AUDIENCE: Gynaecologists who manage common conditions in patients with infertility. SUMMARY STATEMENTS: RECOMMENDATIONS.

Directive clinique no 435 : Chirurgie minimalement invasive dans les traitements de fertilité.

OBJECTIF: Évaluer les risques et bénéfices de la chirurgie minimalement invasive dans la prise en charge des patientes atteintes d'infertilité et fournir des conseils aux gynécologues qui prennent en charge les problèmes les plus fréquents chez ces patientes. POPULATION CIBLE: Patientes atteintes d'infertilité (incapacité à concevoir après 12 mois de rapports sexuels non protégés) en processus diagnostique ou sous traitement. BéNéFICES, RISQUES ET COûTS: On peut recourir à la chirurgie de la reproduction minimalement invasive pour traiter l'infertilité, améliorer les résultats des traitements de fertilité ou préserver la fertilité. Toutes les interventions chirurgicales comportent des risques et des complications associées. La chirurgie de la reproduction n'améliore pas toujours la fertilité et peut, dans certains cas, compromettre la réserve ovarienne. Toutes les interventions entraînent des coûts, lesquels sont assumés par la patiente ou son assureur. DONNéES PROBANTES: Des recherches ont été faites dans les bases de données PubMed-Medline, Embase, Science Direct, Scopus et Cochrane Library pour répertorier les articles publiés en anglais dans la période de janvier 2010 à mai 2021 (voir les termes de recherche MeSH à l'annexe A). MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant le cadre méthodologique GRADE (Grading of Recommendations Assessment, Development and Evaluation). Voir l'annexe B en ligne (tableau B1 pour les définitions et tableau B2 pour l'interprétation des recommandations fortes et conditionnelles [faibles]). PROFESSIONNELS CONCERNéS: Gynécologues qui prennent en charge les affections courantes chez les patientes atteintes d'infertilité. DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS.

Aspirin for Endometrial Preparation in Patients Undergoing IVF: A Systematic Review and Meta-analysis.

OBJECTIVE: To investigate the effect of aspirin on IVF success rates when used as an adjuvant treatment for endometrial preparation. DATA SOURCES: Relevant publications were comprehensively selected from PubMed, MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to November 15, 2020. STUDY SELECTION: Randomized controlled trials (RCTs) and retrospective cohort studies that used aspirin as an adjuvant treatment for endometrial preparation and reported subsequent pregnancy outcomes were included. Studies were excluded if aspirin was used before and/or during ovarian stimulation. DATA EXTRACTION AND SYNTHESIS: This systematic review and meta-analysis included a total of 7 studies. Risk of bias assessment was based on the methodology and categories listed in the Cochrane Handbook for the RCTs and the Newcastle-Ottawa scale for the retrospective studies. The primary outcome was live birth rate. Summary measures were reported as odds ratios (ORs) with 95% confidence intervals (CIs). There was significant evidence that aspirin for endometrial preparation improved live birth rates (OR  1.52; 95% CI   1.15-2.00). No effect was noted for clinical pregnancy rates (OR  1.37; 95% CI   1.00-1.87); however, aspirin was associated with improved pregnancy rates in a subgroup analysis of patients receiving oocyte donation (OR 2.53; 95% CI 1.30-4.92) and in the sensitivity analysis (OR 1.3; 95% CI   1.02-1.66). No effect of aspirin was found for implantation or miscarriage rates (OR 1.31; 95% CI  0.51-3.36 and OR 0.41; 95% CI  0.02-7.42, respectively). CONCLUSION: These findings support a beneficial effect of aspirin for endometrial preparation on IVF success rates, mainly live birth rates, outside the context of ovarian stimulation. However, this evidence is based on poor quality data and needs to be confirmed with high-quality RCTs.

Evidence-based clinical prioritization of embryos with mosaic results: a systematic review and meta-analysis.

PURPOSE: The purpose of this review and meta-analysis is to standardize the practice of mosaic embryo transfer, based on the current available evidence. METHODS: This is a systematic review and meta-analysis. Relevant studies published were comprehensively selected using PubMed, Medline, Embase, and CENTRAL until 5 March 2021. Prospective and retrospective studies reporting the genetic analysis and clinical outcomes of mosaic embryo transfer were included. Risk of bias assessment was based on the Newcastle-Ottawa scale for the non-randomized studies. The primary and secondary outcomes were combined ongoing pregnancy and live birth rate and miscarriage rate, respectively. RESULTS: There were no differences between low and high mosaic embryos when a cut-off of 40% was used in terms of OP/LBR and SAB. However, low mosaics with a cut-off of 50% compared to high mosaics showed a significantly higher OP/LBR in the NGS but not in the a-CGH group, and a significantly lower risk of SAB. No differences were noted between mosaic monosomies versus trisomies and single versus double mosaics for both OP/LBR and SAB. Finally, segmental mosaics showed a higher OP/LBR and a lower SAB compared to whole chromosomes, and single and double mosaics had a higher OP/LBR compared to complex mosaics. CONCLUSIONS: A cut-off of 50% in defining low versus high mosaic embryos is preferable to a threshold of 40% when using NGS platform. No priority was established for mosaic trisomies over monosomies. Single and double mosaics must be preferred over complex mosaics and segmental mosaics must be preferred over whole chromosome mosaics. These results should be interpreted in the context of specific chromosomes involved in the mosaicism.

Timing therapeutic donor inseminations in natural cycles: human chorionic gonadotrophin administration versus urinary LH monitoring.

This cohort study assessed whether timing therapeutic donor sperm inseminations (TDI) in natural cycles (NC) using ultrasound monitoring and ovulation trigger with human chorionic gonadotrophin (US/HCG) improves cumulative live birth rates (LBR) compared with detection of LH surge with urinary kits (u-LH). It included 232 normo-ovulatory women aged ≤40 years, undergoing 538 TDI in NC between 2011 and 2014. In the u-LH group (113 women, 267 cycles), TDI was performed the day following a positive test. In the US/HCG group (119 women, 271 cycles), ovulation was triggered with HCG when a follicle ≥17 mm was noted, and TDI performed 36 h later. The first three cycles were analysed per patient. Groups were comparable for baseline characteristics. Cumulative LBR were comparable between u-LH and US/HCG groups (31.47% versus 23.11%, respectively) (log-rank test). A generalized estimating equation analysis was performed to compare outcomes per cycle. The LBR per started cycle was comparable between the u-LH and US/HCG groups (12.4% versus 9.2%, respectively). Cancellation rate was significantly higher with u-LH (19.1% versus 11.4%, P = 0.011), but did not impact overall outcomes. In conclusion, urinary LH monitoring is as effective as ultrasound monitoring and ovulation trigger with HCG in TDI performed in NC.

Clomiphene Citrate versus Letrozole for Ovarian Stimulation in Therapeutic Donor Sperm Insemination.

AIM: To compare clomiphene citrate (CC) and letrozole for ovarian stimulation (OS) in therapeutic donor sperm insemination (TDI) cycles. METHODS: Retrospective cohort study between January 2011 and June 2014 at a University-affiliated private IVF clinic in Montreal, Canada. 257 normo-ovulatory women ≤40 years of age with no history of infertility undergoing 590 TDI cycles in the absence of a male partner (single women and same-sex couples) or azoospermia were included. Patients received 100 mg CC daily (145 women, 321 cycles) or letrozole 5 mg daily (112 women, 269 cycles), from days 3 to 7. Only the first 3 cycles were included per patient. Our main outcome measure was cumulative live birth rates (LBR). RESULTS: Baseline characteristics were comparable between the 2 groups. There were no differences in LBR per cycle (16.5% (53/321) vs. 11.5% (31/269), p = 0.08) and cumulative LBR (36.6% (53/145) vs. 27.7% (31/112), p = 0.13), between CC and letrozole, respectively. Multiple pregnancy rate (11.6% (8/69) vs. 8.7% (4/46), p = 0.6) and miscarriage rate (21.7 vs. 21.7%, p = 1) were also comparable between CC and letrozole, respectively. CONCLUSION: In normo-ovulatory women undergoing TDI, OS with CC or letrozole resulted in similar live birth and twin pregnancy rates.

Enhancing surgical performance: the role of robotic surgery in myomectomies, a systematic review and metanalysis.

Examine the role, benefits, and limitations of robotic surgery in myomectomies compared to laparoscopic and open surgical approaches. This review sourced data from CENTRAL, Pubmed, Medline, and Embase up until May 1, 2023. Full articles comparing clinical outcomes of robotic myomectomy with open or laparoscopic procedures were included without language restriction. Initially, 2150 records were found. 24 studies were finally included for both qualitative and quantitative analyses. Two investigators independently assessed all reports following PRISMA guidelines. Meta-analysis was conducted using the software "Review Manager Version 5.4". Risk-of-bias was assessed using the Newcastle-Ottawa scale. Sensitivity analysis was conducted, when feasible. In a comparison between robotic and laparoscopic myomectomies, no significant difference was observed in fibroid weights and the size of the largest fibroid. Robotic myomectomy resulted in less blood loss, but transfusion rates were comparable. Both methods had similar complication rates and operative times, although some robotic studies showed longer durations. Conversion rates favored robotics. Hospital stays varied widely, with no overall significant difference, and pregnancy rates were similar between the two methods. When comparing robotic to open myomectomies, open procedures treated heavier and larger fibroids. They also had greater blood loss, but the robotic approach required fewer transfusions. The complication rate was slightly higher in open procedures. Open surgeries were generally faster, postoperative pain scores were similar, but hospital stays were longer for open procedures. Pregnancy rates were comparable for both robotic and open methods. Robotic surgery offers advancement in myomectomy procedures by offering enhanced exposure and dexterity, leading to reduced blood loss and improved patient outcomes. PROSPERO registration: CRD42023462348.

Pelvic Diagnostic Challenges of Appendiceal Neoplasm Mimicking a Hematosalpinx: A Case Report.

Appendiceal mucinous neoplasms are rare and can be easily misdiagnosed as adnexal masses. Fertility is a concern in cases requiring cytoreductive surgery involving the ovaries and if hyperthermic intraperitoneal chemotherapy is considered. We present the case of a 35-year-old patient with primary infertility who was suspected to have a hematosalpinx on ultrasonography and magnetic resonance imaging (MRI) but was found to have an appendiceal mucinous neoplasm on laparoscopy. Fertility preservation was offered to this patient. Appendiceal mucinous neoplasms should be considered in the differential diagnosis of patients in their reproductive years presenting with adnexal masses. Fertility preservation should be discussed with these patients, especially when gonadotoxic treatments are planned.

The POPI-Plus tool: prediction model of outcome of pregnancy in in vitro fertilization from a large retrospective cohort.

OBJECTIVE: To create a tool that accurately predicts live birth chances after a positive pregnancy test after elective single embryo transfer (ET). DESIGN: Retrospective cohort. SETTING: CHUM hospital and Ovo clinic in Montreal, Canada. PATIENT(S): Patients with a positive pregnancy test result who underwent their first single ET after in vitro fertilization (IVF) at the CHUM hospital and Ovo clinic in Montreal, Canada, from 2012 to 2016 were selected. A total of 1,995 patients were included in this study. INTERVENTION(S): The data from both centers were combined and divided into training (70%, n = 1,398) and validation (30%, n = 597) sets. The predictive model was developed using backward selection method for the following variables: age of patient at egg retrieval; log ß-human chorionic gonadotropin (ß-hCG) (ß-hCG) 1; log ß-hCG 2; and IVF treatment type. Moreover, the classification tree, random forest, and neural network models were generated. MAIN OUTCOME MEASURE(S): The measured outcomes were live birth (live fetus ≥24 weeks of gestation) and nonviable pregnancies. The performance of all models was evaluated by area under the receiver operating characteristic curve (AUC). RESULT(S): Advancing age was negatively correlated with live birth. The odds ratio (OR) of age of patient at the time of egg retrieval was 0.95 (95% confidence interval [CI], 0.91-0.99). The log ß-hCG 1 and log ß-hCG 2 were positively correlated with live birth in the univariate analysis (OR, 4.15 [95% CI, 3.19-5.39], and OR, 3.84 [95% CI, 2.99-4.93], respectively). The ß-hCG 1 level needed for a successful pregnancy was lower in frozen ET and modified natural IVF than in simulated IVF (OR, 0.55 [95% CI, 0.34-0.91], and OR, 0.49 [95% CI, 0.26-0.95], respectively). The best performance in terms of the AUC was the updated logistic model: POPI-Plus. The AUC values were 0.76 (95% CI, 0.73-0.79) and 0.78 (95% CI, 0.74-0.82) for the training and validation data, respectively. The other models (classification tree, random forest, and neural network) also performed adequately, with an AUC of ≥0.7, but remained below POPI-Plus. An open-access calculator was generated and can be found on the website of the University of Montreal on the following link: https://deptobsgyn.umontreal.ca/departement/divisions/medecine-et-biologie-de-la-reproduction/the-popi-plus-tool/. CONCLUSION(S): The POPI-Plus tool offers individualized counseling for patients after an initial positive ß-hCG test result. Future studies will assess its impact on patient anxiety while awaiting viability ultrasound and perform prospective validation on new patients.

An algorithm combining ultrasound monitoring and urinary luteinizing hormone testing: a novel approach for intrauterine insemination timing.

OBJECTIVE: Intrauterine insemination (IUI) is a commonly used treatment for infertility. Optimal timing of insemination is achieved either by ultrasound monitoring of follicular growth followed by the administration of human chorionic gonadotropin (hCG) or by the detection of a luteinizing hormone (LH) surge through urinary LH testing (uLH). However, in cycles where follicular growth is monitored, there is a possibility of a premature LH rise which may affect the outcome of treatment. The objective of the current study was to determine the frequency of spontaneous LH surges in ultrasound-monitored IUI cycles. METHODS: One hundred IUI cycles were followed for this prospective cohort study. In combination with ultrasound monitoring, uLH testing was performed twice daily. A serum LH test was performed in the case of an inconclusive uLH test result. IUI was performed either on the day after a positive LH test or, if the diameter of the dominant follicle reached 18 mm and the LH test was still negative, 36 hours after ovulation triggering by administration of hCG. RESULTS: Of the 87 analyzed cycles, 19 (21.8%) exhibited a premature LH surge as detected by urine testing. Eleven further cycles had an inconclusive urine result, and in six of these (6.9% of cycles) the result was confirmed positive by serum LH testing, giving a total of 25 cycles (28.7%) experiencing a premature LH surge. CONCLUSION: A considerable proportion of patients undergoing ultrasound-monitored IUI cycle had a spontaneous LH surge before ovulation triggering was scheduled. This could affect pregnancy rates following IUI.

Risk factors for the development of endometrial fluid in women undergoing IVF: A retrospective cohort study✰.

RESEARCH QUESTION: Presence of endometrial fluid (EF) is a poorly understood pathology and remains a challenge for clinicians, as very little data exists to explain its consequences and treatment. Our objective was to investigate risk factors for EF during IVF. DESIGN: This retrospective cohort study included all women with a freeze all embryos cycle (FAE) for EF between 2010 and 2016 at a university-affiliated private IVF center. Controls (2:1) were randomly selected out of the database of our fresh autologous IVF cycles during the same period. Main outcome measures were possible risk factors for EF, comprising polycystic ovarian syndrome (PCOS), ovarian hyperstimulation syndrome (OHSS), previous pelvic or endometrial surgery (polypectomy or synechia removal), cesarean section, myomas and severe endometriosis. A logistic regression model was used to assess independent risk factors for EF. RESULTS: Out of 9000 IVF cycles, 1204 were FAE cycles, among which we identified 86 EF cases. We then selected 171 controls. Independent risk factors for presence of EF were a history of previous myomectomy (adjusted odds ratio (aOR) 19.77, 95%CI [4.01-97.53]), severe endometriosis (aOR 5.97, 95%CI [2.09-17.05]), PCOS (aOR 5.72, 95%CI [2.66-12.33]) and previous cesarean section (aOR 5.17, 95%CI [1.84-14.49]). CONCLUSIONS: Our results are not only confirming the association between PCOS, severe endometriosis, previous cesarean procedure and EF, but also reporting for the first time an association between previous myomectomy and EF.

450 IU versus 600 IU gonadotropin for controlled ovarian stimulation in poor responders: a randomized controlled trial.

OBJECTIVE: To compare the outcomes of controlled ovarian stimulation/in vitro fertilization cycles using 450 IU and 600 IU gonadotropin per day in women at risk of poor ovarian response. DESIGN: Prospective randomized controlled nonblinded study. SETTING: University-affiliated private IVF center. PATIENT(S): Women considered to be at risk of poor ovarian response: aged <41 years with basal FSH >10 IU/L, antimüllerian hormone <1 ng/mL, antral follicle count ≤ 8, or a previous IVF cycle with ≥ 300 IU/d gonadotropin that resulted in a cancellation, <8 follicles, or <5 oocytes. INTERVENTION(S): A total of 356 patients underwent a microdose GnRH agonist flare-up IVF/intracytoplasmic sperm injection protocol with a fixed daily dose of either 450 IU FSH (n = 176) or 600 IU FSH (n = 180) equally divided between Menopur and Bravelle. MAIN OUTCOME MEASURE(S): Number of mature oocytes retrieved. RESULT(S): The two groups were similar in terms of age, ovarian reserve, cause of infertility, duration of stimulation, and cycle cancellation rate. There were no significant differences in the number of metaphase II oocytes retrieved (4 [range 0-6] vs. 4 [range 2-7]), fertilization rate (62.4% vs. 57.0%), biochemical pregnancy rate (20.5% vs. 22.9%), clinical pregnancy rate (16.4% vs. 18.3%), and implantation rate (29.8% vs. 30.4%) between the 450 IU and 600 IU groups, respectively. CONCLUSION(S): Gonadotropin of 600 IU/d does not improve outcome of IVF cycles compared with 450 IU/d in women at risk of poor ovarian response. CLINICAL TRIAL REGISTRATION NUMBER: NCT00971152.