The Blastulation Rate Is Negatively Associated With Euploid Rate.

OBJECTIVES: To study the association between the blastulation rate, the presence of 1 pronucleus (1PN) zygotes, and the ploidy of the cohort of blastocysts. METHODS: A cross-sectional study using the existing databases of 2 university fertility centres in Canada. We included 345 cycles from 235 couples who underwent next-generation sequencing preimplantation genetic testing for the detection of aneuploidy in the study. RESULTS: A total of 1456 blastocysts were biopsied. In multivariate analysis, only female age and the number of 1PN/2PN embryos showed a negative association with euploid ratio. Surprisingly, when the analysis was limited to cycles with no delayed blastulation, the blastulation rate was also negatively associated with the euploid ratio. CONCLUSIONS: This study sheds some light on the stages of early embryo development. Further study on the mechanisms governing embryo development and the different cell cycle checkpoints in embryo development is warranted.

Immunomodulation for unexplained recurrent implantation failure: where are we now?

In brief: Immune dysfunction may contribute to or cause recurrent implantation failure. This article summarizes normal and pathologic immune responses at implantation and critically appraises currently used immunomodulatory therapies. Abstract: Recurrent implantation failure (RIF) may be defined as the absence of pregnancy despite the transfer of ≥3 good-quality blastocysts and is unexplained in up to 50% of cases. There are currently no effective treatments for patients with unexplained RIF. Since the maternal immune system is intricately involved in mediating endometrial receptivity and embryo implantation, both insufficient and excessive endometrial inflammatory responses during the window of implantation are proposed to lead to implantation failure. Recent strategies to improve conception rates in RIF patients have focused on modulating maternal immune responses at implantation, through either promoting or suppressing inflammation. Unfortunately, there are no validated, readily available diagnostic tests to confirm immune-mediated RIF. As such, immune therapies are often started empirically without robust evidence as to their efficacy. Like other chronic diseases, patient selection for immunomodulatory therapy is crucial, and personalized medicine for RIF patients is emerging. As the literature on the subject is heterogenous and rapidly evolving, we aim to summarize the potential efficacy, mechanisms of actions and side effects of select therapies for the practicing clinician.

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.

The influence of regulation of medically assisted reproduction on the risk of hospitalization in the first 2 years of life.

STUDY QUESTION: Do publicly funded fertility treatment and single embryo transfer (SET) result in lower hospitalization rates of children of parents with infertility? SUMMARY ANSWER: Following the 2010 Quebec law introducing free fertility treatment and SET, neonatal intensive care unit (NICU) admissions decreased among all children born to parents with infertility, but not among singletons, whose risk remained slightly higher than that of children of parents without infertility, even accounting for treatment and maternal age. WHAT IS KNOWN ALREADY: Previous studies reported lower NICU admission rates among children conceived with ART after the 2010 law; however, children conceived without ART by parents with infertility were not considered. STUDY DESIGN, SIZE, DURATION: Cohort study of children born in 1997-2017 to patients evaluated for infertility ('exposed') at an academic fertility center in Montreal (Canada) in 1996-2015. A random sample of births to Montreal residents served as comparison. Outcomes were identified from Quebec administrative databases. PARTICIPANTS/MATERIALS, SETTING, METHODS: We compared children's healthcare utilization before and after the 2010 law in 6273 exposed and 12 583 randomly sampled births (6846 and 12 775 children, respectively). We repeated the analysis among children conceived in the 63 months before and after the law ('restricted period'), and examined whether differences in twinning, fertility treatment, and maternal age explained the higher risk of NICU admission among children of parents with infertility. MAIN RESULTS AND THE ROLE OF CHANCE: In the exposed cohort, the proportion of twin births and of several adverse outcomes declined after the law. NICU admission and duration of NICU stay decreased overall, but not in singletons. Both measures remained higher in exposed children. Except for NICU admission, hospitalization rates were similar in exposed and random sample children. After accounting for fertility treatment and maternal age, exposed singletons were 17% more likely to be admitted to the NICU than children of parents with no medical history of infertility. LIMITATIONS, REASONS FOR CAUTION: Sample size was relatively small; infertile patients were from a single center and the random sample from one city. Despite some limitations, administrative databases are likely to accurately reflect healthcare utilization. WIDER IMPLICATIONS OF THE FINDINGS: Universal access to treatment and, particularly, SET results in an overall reduction of adverse outcomes among children conceived with treatment; however, children of parents with infertility are at a slightly higher risk, regardless of treatment. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Canadian Institutes for Health Research (CIHR, grant no. 123362). No competing interests. TRIAL REGISTRATION NUMBER: N/A.

Is There an Association Between Sperm Parameters and Sexual Orientation? A Cross Sectional Study.

OBJECTIVE: To evaluate whether sexual orientation affects sperm parameters. METHODS: This was a cross-sectional study using existing data from an academic reproductive centre for the period of April 01, 2009, to March 31, 2021. We compared the results of sperm analysis from male patients who were in same-sex relationships (study group) with those of men in heterosexual relationships who did not have male-factor infertility (control group). A subsequently comparison of both groups with World Health Organization (WHO) reference values was also performed. RESULTS: Thirty-nine samples from the study group were compared with 494 samples from the control group. All parameters, apart from morphology, were comparable. The median sperm concentrations were 64 (interquartile range [IQR] 32.1-102.9) million/mL and 50.1 (IQR 25.3-92.5) million/mL in the study and control groups, respectively (P = 0.252), whereas the median percentage of progressive motile sperm was 50% (IQR 34-65) in the study group and 52% (IQR 33-65) in the control group (P = 0.198). The median percentage of morphologically normal sperm was higher in the control group than in the study group (6% vs. 5%; P = 0.019). However, no significant difference was found when sperm morphology was dichotomized with the cut-off of ≥4% (74.1% and 74.4%, respectively; P = 0.966). When compared with the WHO reference group, the percentage of men with total motile sperm counts ≥10 million and the percentage of men with normal morphology were significantly lower in both groups. CONCLUSION: Our study suggests that there is no relationship between sexual orientation and sperm parameters.

Hereditary breast cancer and fertility preservation outcomes.

PURPOSE: To determine the frequency of hereditary breast cancer associated with different mutated genes and to evaluate fertility preservation (FP) outcomes among young women with hereditary breast cancer when compared to non-hereditary breast cancer. MATERIAL AND METHODS: A retrospective cohort study of women with breast cancer who underwent fertility preservation treatment at our academic fertility center between 2005 and 2019. We included all women with breast cancer aged < 40 years who had a genetic testing and underwent fertility preservation before starting gonadotoxic therapy (n = 132). Our objective was to evaluate the total number of oocytes retrieved, mature oocytes MII, embryos (where appropriate), cryopreserved oocytes, and/or embryos. RESULTS: Of 132 women with breast cancer, 40 women were found to be genetically positive (31.4%), 31 women of 40 (77.5%) had a BRCA mutation, 3 (7.5%) had ATM, 2 (5%) had CHK2, and one (2.5%) for each of the following genes: PALP2, NF, MUTYH.c.536A, and TP53. There was no significant difference between the groups in the total number of eggs retrieved and the number of MII oocytes and cryopreserved oocytes. The numbers of fertilized oocytes and cryopreserved embryos in the hereditary (n = 40) and non-hereditary (n = 92) group were (5.15 ± 6.6 vs 2.90 ± 4.2, P = 0.054) and (3.35 ± 3.7 vs 1.9 ± 2.8, P = 0.046) respectively. CONCLUSION: More than three quarters of positive mutated genes in women with breast cancer are BRCA mutations. Compared to those with non-hereditary breast cancer, women with hereditary breast cancer attained higher number of cryopreserved embryos.

Effects of embryo retention during embryo transfer on IVF outcomes.

PROPOSE: To investigate embryo retention (ER) rate in embryo transfer (ET) cycles and its effects on reproductive outcomes in a large database. METHODS: A matched retrospective cohort study in a tertiary academic hospital-based reproductive center. A total of 15,321 ET cycles were performed from January 2008 to December 2018. Each woman was matched with three separate control subjects of the same age (± 1 year), embryo condition, main causes of infertility, and type of protocol used for fresh or frozen ET cycles. The main outcomes were ER rate, and implantation, clinical pregnancy, ectopic pregnancy, and live birth rates. RESULTS: The overall incidence of ER was 1.4% (213/15,321). There was no difference in the rate of ER rate in fresh ET cycles compared with frozen transfer cycles (P = 0.54). We matched 188/213 (88%) of cases in the ER group to 564 non-ER cases. There were no cases of the blood in the catheter seen in the ER group. Pregnancy outcomes were similar between the ER and the non-ER cycles: clinical pregnancy rate (31.3% vs. 36.1%, P = 0.29), implantation rate (26.2% vs. 31.3%, P = 0.2), live birth rate (20.3% vs. 24%, P = 0.53), ectopic pregnancy rate (0.5% vs. 0.4%, P = 0.18), and miscarriage rate (10.7% vs. 11.3%, P = 0.53). CONCLUSION: Our results suggest that ER rate does not affect the reproductive outcomes including clinical pregnancy rate, implantation rate, and live birth rate. Patients and physicians should not be concerned about the retention of embryos during transfer since there is no effect on pregnancy outcome.

Does increasing estrogen dose during frozen embryo transfer affect pregnancy rate?

OBJECTIVE: To assess the effect of increasing estrogen doses during hormone therapy frozen embryo transfer (HT-FET) cycles on endometrial thickness and success rates compared to patients who received fixed estrogen dose. MATERIALS AND METHODS: A retrospective study from a university-based fertility clinic during the years 2008-2021. We compared two groups: the fixed-dose group (i.e., received 6 mg estradiol dose daily until embryo transfer) and the increased-dose group (i.e., the initial estradiol dose was 6 mg daily, and was increased during the cycle). PRIMARY OUTCOME: clinical pregnancy rate. RESULTS: The study included 5452 cycles of HT-FET: 4774 cycles in the fixed-dose group and 678 cycles in the increased-dose group. Ultrasound scan on days 2-3 of the cycle showed endometrial thickness slightly different between the two groups (4.2 mm in the fixed-dose and 4.0 mm in the increased-dose group, P = 0.003). The total estrogen dose was higher, and the treatment duration was longer in the increased than the fixed-dose group (122 mg vs. 66 mg and 17 days vs. 11 days, respectively; P < 0.001). The last ultrasound scan done before the addition of progesterone showed that the endometrial thickness was significantly thicker in the fixed than the increased-dose group (9.5 mm vs. 8.3 mm; P < 0.001). The clinical pregnancy rates were 35.8% in the increased-group vs. 34.1% in the fixed-dose group; P = 0.401. CONCLUSIONS: The increased-dose group had thinner endometrium despite the higher doses of estrogen and longer treatment duration than the fixed-dose group. However, the pregnancy rates were similar between the two groups.

A comparison of frozen-thawed embryo transfer protocols in 2920 single-blastocyst transfers.

OBJECTIVE: To assess the effect of frozen-thawed embryo transfer (FET) protocol on live-birth rate (LBR) and clinical pregnancy rate (CPR), in single-vitrified-blastocyst transfer MATERIALS AND METHODS: Retrospective cohort study with FET of a single-blastocyst embryos (n = 2920 cycles) thawed 2013-2018. FET protocols were natural cycles (NC-FET) (n = 147), artificial hormone replacement treatment cycles (HRT-FET) (n = 2645), and modified NC (mNC) with hCG triggering (n = 128). Primary outcome was LBR. Adjustment for age, embryo grade, year of freezing\thawing, infertility cause, and endometrial thickness was performed. RESULTS: There were no significant differences between the groups with regard to female age, embryo grade, and endometrial thickness. LBR was higher in the mNC compared to HRT-FET cycles (38.3% vs. 20.9% P < 0.0001), and in the NC compared to HRT-FET cycles (34.7% vs. 20.9%, P = 0.0002). CPR was higher in the mNC compared to HRT-FET cycles (46.1% vs. 33.3% P = 0.0003), and in the NC compared to HRT-FET cycles (45.9% vs. 33.3%, P = 0.002). There was no significant difference in LBR or CPR between NC-FET and mNC-FET. Higher LBR with NC-FET and mNC-FET remained significant after adjusting for confounders (aOR 2.42, 95%CI 1.53-3.66, P < 0.0001). CONCLUSION: The use of the convenient artificial HRT-FET cycles must be cautiously reconsidered in light of the potential negative effect on LBR when compared with natural cycle FET.

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.

Correction: Comprehensive analysis of 204 sporadic hydatidiform moles: revisiting risk factors and their correlations with the molar genotypes.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Comprehensive analysis of 204 sporadic hydatidiform moles: revisiting risk factors and their correlations with the molar genotypes.

Hydatidiform mole (HM) is an aberrant human pregnancy characterized by excessive trophoblastic proliferation and abnormal embryonic development. HM has two morphological types, complete (CHM) and partial (PHM), and non-recurrent ones have three genotypic types, androgenetic monospermic, androgenetic dispermic, and triploid dispermic. Most available studies on risk factors predisposing to different types of HM and their malignant transformation mainly suffer from the lack of comprehensive genotypic analysis of large cohorts of molar tissues combined with accurate postmolar hCG follow-up. Moreover, 10-20% of patients with one HM have at least one non-molar miscarriage, which is higher than the frequency of two pregnancy losses in the general population (2-5%), suggesting a common genetic susceptibility to HM and miscarriages. However, the underlying causes of the miscarriages in these patients are unknown. Here, we comprehensively analyzed 204 HM, mostly from patients referred to the Quebec Registry of Trophoblastic Diseases and for which postmolar hCG monitoring is available, and 30 of their non-molar miscarriages. We revisited the risk of maternal age and neoplastic transformation across the different HM genotypic categories and investigated the presence of chromosomal abnormalities in their non-molar miscarriages. We confirm that androgenetic CHM is more prone to gestational trophoblastic neoplasia (GTN) than triploid dispermic PHM, and androgenetic dispermic CHM is more prone to high-risk GTN and choriocarcinoma (CC) than androgenetic monospermic CHM. We also confirm the association between increased maternal age and androgenetic CHM and their malignancies. Most importantly, we demonstrate for the first time that patients with an HM and miscarriages are at higher risk for aneuploid miscarriages [83.3%, 95% confidence interval (CI): 0.653-0.944] than women with sporadic (51.5%, 95% CI: 50.3-52.7%, p value = 0.0003828) or recurrent miscarriages (43.8%, 95% CI: 40.7-47.0%, p value = 0.00002). Our data suggest common genetic female germline defects predisposing to HM and aneuploid non-molar miscarriages in some patients.

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.

Effect of newborn gender on placental histopathology and perinatal outcome in singleton live births following IVF.

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.

Is intrauterine insemination a viable treatment option for women over 43 years old? An analysis by ovarian stimulation protocol and sperm source.

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.

Outcomes of ovarian stimulation and fertility preservation in breast cancer patients with different hormonal receptor profiles.

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.

Impact of intramural non-cavity-distorting leiomyoma on placental histopathology and perinatal outcome in singleton live births resulting from in vitro fertilization treatment.

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.

Effects of cancer stage and grade on fertility preservation outcome and ovarian stimulation response.

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.

The management of unexplained infertility: an evidence-based guideline from the Canadian Fertility and Andrology Society.

Unexplained infertility is a common diagnosis affecting as many as 50% of couples seeking infertility care. As a diagnosis of exclusion, its treatment remains largely empirical. Historically, a step-wise progression in treatment has been initiated with the least invasive, least expensive option followed by a gradual progression to therapies using assisted reproductive technology. In recent years there have been advocates for more rapid-progression IVF. This guideline from the Canadian Fertility and Andrology Society (CFAS) provides comprehensive, evidence-based recommendations for the treatment of unexplained infertility, including expectant management, laparoscopy, intrauterine insemination (IUI) alone, ovarian stimulation with oral agents or gonadotropins alone, ovarian stimulation + IUI, and IVF. The quality of supporting evidence for each recommendation is evaluated using the framework outlined by the Canadian Task Force on Preventive Health Care. This guideline recognizes that the therapeutic approach should be individualized taking into account patient age and duration of infertility, and emphasizes those strategies that are most likely to result in a healthy live birth.

Treatment of hydrosalpinx in relation to IVF outcome: a systematic review and meta-analysis.

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.