Histopathological profile of women who had previously failed in-vitro fertilization and the association to the outcome in the subsequent in-vitro fertilization cycle.

OBJECTIVE: To evaluate the endometrial histopathological profile of patients undergoing curettage and the association of the histopathological profile with the pregnancy outcome during the subsequent in-vitro fertilization (IVF) cycle. METHODS: In this retrospective cohort study, a total of 248 women with at least one failed attempt of IVF and who underwent curettage and a subsequent IVF were included. Demographic data, endometrial histopathological records, stimulation information, and pregnancy outcomes were collected and analyzed. RESULTS: The histopathological analysis of endometrial tissues showed that 130 women (52.4%) had endometrial pathologies. Of these women, 103 (41.5%) had endometrial polyps, 22 (8.9%) had chronic endometritis, and five (2.0%) had both polyps and endometritis. No statistical difference was observed between the normal histopathology group and the abnormal histopathology group in the outcome of the subsequent IVF cycle. Subgroup analyses were performed to further characterize and compare women with normal histopathology and women with endometrial polyps (polyp subgroup) or chronic endometritis (endometritis subgroup). No statistical differences were found among the three groups in the rates of pregnancy (44.1% vs. 49.5% vs. 45.5%, P=0.72), biochemical pregnancy loss (13.5% vs. 15.7% vs. 20.0%, P=0.86), clinical pregnancy loss (25.0% vs. 31.4% vs. 30.0%, P=0.77), and live birth (27.1% vs. 26.2% vs. 22.7%, P=0.91) during the subsequent IVF cycle. CONCLUSION: Women with previously failed IVF and abnormal endometrial histopathology treated with curettage had the same outcome in the subsequent IVF cycle as women with normal endometrial histopathology.

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.

Effect of uterine dimensions on live birth rates after single embryo transfer in infertile women.

RESEARCH QUESTION: Do uterine size parameters measured by baseline transvaginal ultrasound predict live birth after single embryo transfer (SET) of a high-quality blastocyst? DESIGN: Retrospective cohort study including women undergoing their first SET between August 2010 and March 2014 at a large university hospital reproductive centre. The effects of baseline uterine dimensions on live birth rate (LBR) were analysed while controlling for confounding effects. RESULTS: A total of 437 nulliparous and 70 parous women were included. The nulliparous group had lower body mass index (BMI) (24.4 ± 5.1 versus 25.9 ± 4.5 kg/m2; P = 0.015) and a higher number of fibroids (0.4 ± 1.0 versus 0.2 ± 0.5; P = 0.005) than the parous group. While controlling for confounding effects, none of the uterine parameters appeared to be a significant predictor of LBR among nulliparous and parous women (P > 0.05 in all cases). A subsequent analysis of endometrial length was done, whereby the endometrial lengths were divided into quartiles (20.0-32.2 mm; 32.3-36.5 mm; 36.6-40.0 mm; 40.1-54.0 mm). After controlling for confounders, the shortest quartile in the nulliparous group had a significantly lower LBR (P = 0.02) than the other groups. Receiver operating characteristic curves suggested that endometrial cavity length and cervical length did not aid clinically. CONCLUSION: Uterine parameters do not have a clinically useful impact on LBR after SET of a blastocyst in infertile women. The use of baseline endometrial length to predict live birth is no better than chance, while cervical length only predicts failure to live birth.

A comparison of IVF outcomes transferring a single ideal blastocyst in women with polycystic ovary syndrome and normal ovulatory controls.

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

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.

Chronic Endometritis in Fertile and Infertile Women Who Underwent Hysteroscopic Polypectomy.

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

Use of cabergoline and post-collection GnRH antagonist administration for prevention of ovarian hyperstimulation syndrome.

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

Effect of GnRH agonist and letrozole treatment in women with recurrent implantation failure.

OBJECTIVE: To compare the influence of dual suppression with the use of GnRH agonist plus aromatase inhibitor compared with suppression with the use of GnRH agonist alone or no suppression at all in patients with idiopathic recurrent implantation failure (RIF). DESIGN: Retrospective cohort study. SETTING: University-affiliated reproductive center. PATIENT(S): A total of 523 infertile women who failed two blastocyst transfers underwent a third frozen blastocyst transfer. Women with known endometriosis were excluded. INTERVENTION(S): A total of 204 subjects were not pretreated, 143 received 2 months of GnRH agonist (3.75 mg intramuscular leuprolide acetate monthly) only, and 176 received GnRH agonist and aromatase inhibitor (5 mg oral letrozole daily for 60 days). Demographic and stimulation information was collected and cycle outcomes reported. MAIN OUTCOME MEASURE(S): Clinical pregnancy rates. RESULT(S): Age, antral follicle count, basal FSH levels, duration of infertility, previous pregnancies, and full-term deliveries were similar (P>.05). Clinical pregnancy rates were higher among women who received GnRH agonist plus letrozole compared with women who received GnRH agonist only or women without pretreatment (63%, 42%, and 40%, respectively; P<.0001). Live birth rates were higher among women who received GnRH agonist plus letrozole compared with the other groups (56%, 36%, and 34%; P<.0001). No differences in pregnancy outcomes were noted between patients who did not receive pretreatment and those in the GnRH agonist only group. CONCLUSION(S): In patients with RIF, treatment with a GnRH agonist plus letrozole may improve live birth rates in subsequent cycles. We hypothesize that this improvement is due to alterations in the endometrium receptivity or treatment of undiagnosed endometriosis.

NKp44 and NKp30 splice variant profiles in decidua and tumor tissues: a comparative viewpoint.

NKp44 and NKp30 splice variant profiles have been shown to promote diverse cellular functions. Moreover, microenvironment factors such as TGF-ß, IL-15 and IL-18 are able to influence both NKp44 and NKp30 splice variant profiles, leading to cytokine-associated profiles. Placenta and cancerous tissues have many similarities; both are immunologically privileged sites and both share immune tolerance mechanisms to support tissue development. Therefore, we studied the profiles of NKp44 and NKp30 splice variants in these states by comparing (i) decidua from pregnancy disorder and healthy gestation and (ii) matched normal and cancer tissue. Decidua samples had high incidence of both NKp44 and NKp30. In cancerous state it was different; while NKp30 expression was evident in most cancerous and matched normal tissues, NKp44 incidence was lower and was mostly associated with the cancerous tissues. A NKp44-1dominant inhibitory profile predominated in healthy pregnancy gestation. Interestingly, the NKp44-2/3 activation profile becomes the leading profile in spontaneous abortions, whereas balanced NKp44 profiles were observed in preeclampsia. In contrast, a clear preference for the NKp30a/b profile was evident in the 1st trimester decidua, yet no significant differences were observed for NKp30 profiles between healthy gestation and spontaneous abortions/preeclampsia. Both cancerous and matched normal tissues manifested balanced NKp30c inhibitory and NKp30a/b activation profiles with a NKp44-1dominant profile. However, a shift in NKp30 profiles between matched normal and cancer tissue was observed in half of the cases. To summarize, NKp44 and NKp30 splice variants profiles are tissue/condition specific and demonstrate similarity between placenta and cancerous tissues.

Obstetric and neonatal outcome in patients with anxiety disorders.

OBJECTIVE: To investigate whether a diagnosis of anxiety disorder is a risk factor for adverse obstetric and neonatal outcome. METHODS: A retrospective population-based study was conducted comparing obstetric and neonatal complications in patients with and without a diagnosis of anxiety. Multivariable analysis was performed to control for confounders. RESULTS: During the study period 256,312 singleton deliveries have occurred, out of which 224 (0.09%) were in patients with a diagnosis of an anxiety disorder. Patients with anxiety disorders were older (32.17 ± 5.1 versus 28.56 ± 5.9), were more likely to be smokers (7.1% versus 1.1%) and had a higher rate of preterm deliveries (PTD; 15.2% versus 7.9%), as compared with the comparison group. Using a multiple logistic regression model, anxiety disorders were independently associated with advanced maternal age (OR 1.087; 95% CI 1.06-1.11; p = 0.001), smoking (OR 4.51; 95% CI 2.6-7.29; p = 0.001) and preterm labor (OR 1.92; 95% CI 1.32--2.8; p = 0.001). In addition, having a diagnosis of an anxiety disorder was found to be an independent risk factor for cesarean section (adjusted OR 2.5; 95% CI 1.82-3.46; p < 0.001), using another multivariable model. No association was noted between anxiety disorders and adverse neonatal outcomes including small for gestational age, low Apgar scores and perinatal mortality. CONCLUSION: Anxiety disorders are independent risk factors for spontaneous preterm delivery and cesarean section, but in our population it is not associated with adverse perinatal outcome.