Tubal Infertility Research Articles

P-309 Endometriosis does not compromise early embryonic development as well as live birth: a retrospective analysis of 716 standard in vitro fertilization cycles

Abstract Study question Does endometriosis compromise early embryonic development and/or clinical outcome in standard in vitro fertilization (sIVF) cycles? Summary answer Endometriosis does not compromise embryo development or clinical outcome in sIVF cycles characterised by normal semen parameters. What is known already IVF is an elective approach to overcome endometriosis-related infertility. The notion that IVF outcomes are altered in women with endometriosis the is scarce and conflicting. Different meta-analyses reached diverging conclusions concerning a possible impact of endometriosis on clinical outcome. With reference to laboratory outcomes, a reduced fertilization rate with sIVF was observed in several but not all studies. Study design, size, duration A retrospective analysis of 716 women undergoing their first sIVF cycles from 2015 to February 2021, 205 with in situ endometrioma (class IV) and 511 with tubal factor infertility. Participants/materials, setting, methods Diagnosis of endometriosis was based on ultrasound observation of cysts on at least two occasions at least two menstrual cycles apart. Women carrying atypical lesions, i.e., cysts with sonographic appearance compatible but not distinctive for endometriosis, were excluded. Multivariate analysis was conducted using the generalized estimating equation (GEE) approach, thus making it possible the analysis of variables with non-normal distribution. The primary study outcome was live birth rate. Main results and the role of chance After adjustment for maternal, paternal age, maternal body mass index (BMI), anti-mullerian hormone (AMH) and follicle stimulating hormone (FSH) we found no significant difference in fertilization rate [78,69 ± 26,16 (Endo) Vs 79,5 ± 24,01 (Tubal)], embryo quality [33,33 (0 – 57,86) endometriosis vs. 33,40 (0 – 67,70) tubal factor], blastulation rate [52,00 ± 15,01 (endometriosis) vs. 55,49 ± 14,98 (tubal factor)], top quality blastocyst [38,15 ± 18,67 (endometriosis) vs. 34,62 ± 14,77 (tubal factor)], ongoing pregnancy [OR = 0,84, 95% CI (0,54 – 1,32)], live birth [OR = 0,89, 95% CI (0,53 – 1,48)], and miscarriage rate [OR = 0,68, 95% CI (0,27 – 1,74)]. The only significantly different outcome was the percentage of embryos with ≥ 8 blastomeres on day 3 [25,00 (0 - 60,00) endometriosis Vs 40,00 (0 - 67,00) tubal factor]. Limitations, reasons for caution The retrospective design of the study and lack of data on cumulative live birth rates are additional limitations. Wider implications of the findings The results of our study suggest that in women with endometriosis fertilization rate, embryo quality, blastulation rate and live birth rate are not affected in sIVF cycles. Trial registration number N.A.

P-570 Prokineticin-1 follicular fluid levels are strongly associated with diminished ovarian reserve and poor ovarian response: A prospective observational study

Abstract Study question Are Prokineticin-1 (PROK1) follicular fluid (FF) levels associated with poor ovarian response (POR) as well as with other well-known biomarkers associated with ovarian reserve status? Summary answer Poor responders present with increased PROK1 FF levels. Also, PROK1 FF levels are negatively correlated with anti-müllerian hormone (AMH) levels and number of oocytes retrieved. What is known already Prokineticin-1 is an angiogenic factor with pleiotropic properties. Considering its role in reproduction, PROK1 mediates significant angiogenic functions in the fetal-maternal interface. Thus, alterations in PROK1 expression and/or function lead to placenta-derived pregnancy complications. Recently published studies also indicate that PROK1 is associated with ovarian function and oocyte competence. However, limited data associating PROK1 with POR are published. This study uniquely investigates possible associations between PROK1 FF levels in POR cases, with stimulation outcome, as well as with FF levels of other factors related to ovarian functionality, namely VEGF, bone morphogenetic protein 15 (BMP-15) and Pigment Epithelium Derived Factor (PEDF). Study design, size, duration This prospective-observational study was collaboratively conducted between November 2020 and July 2021 at Genesis Athens Clinic and at the University of Athens Medical School. A total of 64 patients undergoing IVF treatment were enrolled. The study group comprised of 32 POR patients defined according to the Bologna criteria. The control group consisted of 32 normal responder women undergoing IVF due to tubal factor and/or mild male factor infertility. Patients with other infertility aetiologies were excluded. Participants/materials, setting, methods Participants in both groups received the standard short GnRH-antagonist protocol. Prior to ovarian stimulation, participants were subjected to basic infertility investigation, including antral follicle count and AMH levels evaluation. The FF samples were collected as part of the oocyte retrieval process, then centrifuged and stored at -80 °C till analysis. Follicular fluid levels of PROK1, VEGF, BMP-15 and PEDF were evaluated via ELISA employing commercially available kits. Statistical analysis was performed employing R Programming Language. Main results and the role of chance Significantly higher PROK1 (3229.63 ± 2372.66 vs 1945.95 ± 1408.01 pg/ml; P-value<0.0001), VEGF (2309.63 ± 412.49 vs 2013.22 ± 330.16 pg/ml; P-value=0.006) and lower BMP-15 (434.13 ± 106.38 vs 532.5 ± 108.26 pg/ml; P-value=0.001) levels were recorded in the POR group. No difference was observed regarding PEDF levels (7.43 ± 1.95 vs 8.23 ± 2.54 ng/ml; P-value=0.2). However, the POR group presented with lower PEDF/VEGF ratio (3.33 ± 1.08 vs 4.18 ± 1.41; P-value=0.02), indicating a reduced antioxidant capacity. PROK1 levels were negatively correlated with AMH (P-value=0.04), number of oocytes retrieved (P-value=0.001) and number of MII oocytes (P-value=0.005). BMP-15 was positively correlated with number of oocytes retrieved (P-value<0.001), number of MII oocytes (P-value=0.002), number of normally fertilized zygotes (P-value=0.007), number of cleavage stage embryos (P-value=0.03) and number of blastocysts (P-value=0.04). VEGF was negatively correlated with AMH (P-value=0.004) and number of oocytes retrieved (P-value=0.03). These correlations remained significant when adjusting for ovarian response status. PROK1 levels, with a cut-off value of 2854.25 pg/ml, were able to predict ovarian response status with an area under the curve at 0.64. Sensitivity was 0.55, specificity was 0.88, and accuracy was 0.71. The positive and negative predictive values were 81.82% and 66.67%, respectively. Limitations, reasons for caution Limitations of our study refer to the limited size of the studied population, as well as to the lack of data considering pregnancy outcomes. Moreover, molecular data with regards to the possible role of PROK1 on POR pathogenesis are required. Future studies are needed to verify the results presented herein. Wider implications of the findings Data presented herein indicate that PROK1 FF levels are strongly associated with diminished ovarian reserve and POR. Considering that FF-PROK1 presents with a similar profile with FF-VEGF, we can form the hypothesis that the compromised angiogenesis observed in POR patients leads to PROK1 and VEGF increase via a negative-feedback-loop. Trial registration number Not applicable

P-633 Poor ovarian response: what are the implications for developmental and genetic health of embryos?

Abstract Study question Are patients with a low ovarian response more likely to develop embryos with chromosomal alterations? Summary answer Low ovarian response has an impact on embryonic development and the genetic normality rate of embryos. What is known already Low ovarian response is characterized by a reduction in the follicular response resulting in a reduced number of eggs. This fact has an impact on the outcome of assisted reproduction treatments. Therefore, understanding the genetic behavior of the embryos of these patients is still a great challenge for both the clinic and the in vitro fertilization laboratory, because, with a better understanding of the embryo's genetic segregation process, it will be possible to apply more assertive behaviors in the human reproduction routine. Study design, size, duration This retrospective cross-sectional study included 73 patients up to 35 years old, splitted into two groups. The poor ovarian responder group (n = 32) and the controls (n = 41). The study group included patients with poor ovarian response, less than six MII oocytes after ovarian punction. The control group was selected according to the following inclusion criteria: the presence of tubal factor unexplained infertility, or adenomyosis. The data were collected between January 2019 and December 2021. Participants/materials, setting, methods All patients included in the study (n = 73) underwent the same assisted reproduction treatment with embryos transferred after biopsy and PGT-A. The T-Students test was applied to compare numerical variables and the q-square test for categorical variables. All the analysis was performed in SPSS software (V26). Patients who had other factors associated with poor ovarian response were excluded. Main results and the role of chance In the comparison between the groups, the differences in the levels of AMH, progesterone, and the number of oocytes in MII were observed, as expected for the two groups (p < 0.05). However, the control group had a higher rate of chromosomally normal embryos when compared to patients with a low ovarian response (60.9%± 30.1 vs 37.6%± 39.7, p = 0.0057) respectively. The other variables such as age, FSH, LH, BMI, estradiol, fertilization rate, rate of blastocyst formation, and quality of blastocysts did not show statistically significant differences. Limitations, reasons for caution Preliminary results with a low number of patients. Wider implications of the findings Patients with a low ovarian response may have lower rates of embryonic chromosomal normality, this fact is important for the indication of genetic testing for these couples. Future prospective studies should be carried out with a larger number of patients to understand the mechanisms that cause genetic alterations in embryos. Trial registration number non applicable

P-484 Oocytes quality assessment in breast cancer: implications for fertility preservation

Abstract Study question Does the breast cancer (BC) influence the oocyte quality and ovarian response to controlled ovarian hyperstimulation (COH) for fertility preservation (FP) in female oncology patients? Summary answer The diagnosis of breast cancer does not seem to be associated with an impairment of ovarian reserve, but with a worsening of oocyte quality. What is known already Fertility preservation in female oncology patients should be integrated as part of management of cancer patient to improve their quality of life. Every day in Italy about 30 new cases of cancer are diagnosed in patients with age under 40 years and BC is the most common malignancy in women undergoing fertility preservation. Currently mature oocyte cryopreservation is a standard technique for fertility. The studies on the outcome of ovarian response after ovarian stimulation in specific cancer patients are limited. Only few reports have suggested a deleterious impact of the oncological disease on quality of follicular growth and ovarian function. Study design, size, duration This is a retrospective single-center case-control study carried out in the IVF (in vitro fertilization) Unit at the Sandro Pertini Hospital in Rome between 2016 and 2021. The aim of this study is to investigate the effect of BC on number, above all on quality of oocyte and on dysmorphic oocyte ratio, in oncology patients compared to women age- and date-matched controls undergoing COH for IVF for male or tubal factor infertility. Participants/materials, setting, methods A total of 294 women were enrolled in the study: 105 women affected by breast cancer in the case group and 189 healthy women in the control group. Boths groups were comparable in terms of age, body mass index (BMI) and antimulleran hormone (AMH) value, E2 level at triggering day, total FSH cumulative dose, stage, histotype, BRCA status and hormone receptors. The primary outcome was number and quality of retrievd oocyte from ovarian pick-up (OPU). Main results and the role of chance There were no significant differences in terms of basal fertility indices between the 2 groups: median AMH levels were 2.3 ng/mL in BC patients and 2.8 ng/mL in control group (p = 0.103). The median length of stimulation was 11 days in both groups. The median of total immature oocytes (oocytes MI + germinal vesicle) was 2 in cancer patients and 0 in control group (p < 0.0001). Finally, the median of total dysmorphic oocytes were 1 in cancer group vs 0 (p < 0.0001). The multivariable analysis identified the cancer as risk factors of presence of dysmorphic oocytes (OR (95%CI):3.92 (1.84-8.35). Moreover either in the case and control group age, BMI, AMH, duration of stimulation, E2 level at triggering day, total FSH cumulative dose and, only for BC patients, stage, histotype, BRCA status and hormone receptors were not statistical significantly associated with the presence of dysmophic oocytes. Finally, our data confirmed that the cancer is the only risk factors not only for the presence of dysmorphic oocytes, but also respect to the number of dysmorphic oocytes and to the percentage of dysmorphic oocytes respect to the total number of retrieved oocytes for patient. Two patients have had a spontaneous pregnancy. Limitations, reasons for caution The limitations concern the paucity of specific cancer group especially BRCA mutated BC patients and the different triggers for induction of final maturation. We still have not a follow up data to evaluate the competence of vitrified MII oocytes for oncology patients and we cannot report information on spontaneous births. Wider implications of the findings The BC diagnosis is a four times greater risk factor in retrieving dysmorphic oocytes, but the stage of BC does not influence the number of retrieved dysmorphic oocytes. Further studies are necessary to evaluate the etiopathogenetic mechanisms underlying oocyte abnormalities in specific group of female oncology patients. Trial registration number 0104898/2020

P-590 Discriminatory value of steroid hormones on polycystic ovary syndrome in women with infertility and obesity

Abstract Study question Which steroid hormone (ratio) has the highest discriminatory value in the biochemical diagnosis of polycystic ovary syndrome (PCOS) in women with infertility and obesity? Summary answer Androstenedione (A4) is a potentially useful discriminatory biomarker for PCOS in women with obesity, whereas Testosterone (T)/Dihydrotestosterone (DHT) and 11-oxygenated androgens are not. What is known already The best biomarker to assess biochemical hyperandrogenism in PCOS is still under discussion. Serum total or free T, followed by Free Androgen Index (FAI), and Dehydroepiandrosterone Sulfate (DHEA-S) are the most widely used biomarkers. T/DHT ratio has been proposed as a useful biomarker for PCOS. Moreover, a recent study demonstrated 11-oxygenated androgens represent the majority of circulating androgens in PCOS. Whether this is also relevant in women with obesity is unclear. We aimed to assess the discriminatory value of different steroid hormones and their ratios for PCOS as well as adverse metabolic phenotype within PCOS in women with obesity. Study design, size, duration We used the baseline data and samples originating from an RCT that examined whether a six-month lifestyle intervention prior infertility treatment in women with obesity improved live birth rate, compared to prompt infertility treatment. In total of 577 women with obesity were randomized between 2009 and 2012. Women were diagnosed with PCOS according to the Rotterdam criteria. Metabolic syndrome was diagnosed based on the revised criteria of the National Cholesterol Education Program. Participants/materials, setting, methods Women with PCOS comprised the study group (N = 132). Ovulatory women with idiopathic, tubal or male factor infertility were the control group (N = 83). Women were excluded when blood sampling was performed in the luteal phase or when baseline samples were unavailable. The steroid hormones were measured using LC-MS/MS. 11β-hydroxyandrostenedione (11OHA4) and 11-ketotestosterone (11KT) were analyzed using LC-MS/MS in a separate method. The discriminatory value was based on receiver operator characteristic (ROC) curves with adjustment for age. Main results and the role of chance The mean age was 28.1 years in the PCOS group and 30.9 years in the control group (p < 0.001). BMI was not significantly different (36.0±3.2 versus 35.7±3.5, p = 0.51). Among the tested steroid hormones (ratios), SHBG, A4, T, DHT, 11KT, FAI, T/DHT ratio, and T/A4 ratio showed statistically significant differences between the PCOS and the control group. DHEA, DHEA-S, 11OHA4 did not differ between the groups. The crude AUCs of FAI, T, A4, T/DHT ratio, SHBG, 11KT, T/A4 ratio, and DHT in ROC analysis for representing PCOS were 0.85, 0.84, 0.81, 0.70, 0.62, 0.59, 0.58, and 0.57 respectively. Among the markers with crude AUCs≥0.70, the incremental value of the marker A4 (AUC difference: 0.14, 95%CI: 0.07 to 0.21), T (0.18, 95%CI: 0.10 to 0.25), and FAI (0.18, 95%CI: 0.10 to 0.25) in addition to age showed significant improvement, but T/DHT ratio (0.02, 95%CI: –0.01 to 0.04) did not. However, the combination of A4 together with T or FAI did improve discriminatory value of individual T or FAI (AUC difference: –0.001, 95%CI: –0.004 to 0.003 and 0.007, –0.007 to 0.02, respectively). None of the measured steroid hormones (ratios) have promising discriminatory value for adverse metabolic phenotype within PCOS in women with obesity. Limitations, reasons for caution This is a post-hoc analysis and no power calculation was performed. There was a significant difference in age between women with and without PCOS, and residual confounding might exist. All PCOS patients in this analysis were infertile and obese, and it is conceivable that milder PCOS phenotypes are not represented. Wider implications of the findings T/DHT ratio and 11-oxygenated androgens might not serve as a promising discriminatory biomarker for PCOS in women with obesity, nor for adverse metabolic phenotype within PCOS in these women. A4 is a potential biomarker for PCOS diagnosis in women with infertility and obesity, however, its utility potency needs further validation. Trial registration number NTR 1530

A study on histopathological changes in ectopic tubal gestation

Background: Ectopic pregnancy is a serious cause of maternal morbidity and mortality. Fallopian tube is the most common site. Ectopic pregnancy is often the consequence of chronic salpingitis. The aim of the study was to identify the various histopathological changes in the fallopian tube, which are removed following an ectopic tubal gestation. The prevalence of various risk factors in ectopic tubal pregnancy was also investigated. Methods: This descriptive study included 160 cases of ectopic tubal gestation received in the department during the study period. Slides were studied for various changes like chronic salpingitis, acute salpingitis, salpingitis isthmica nodosa, endometriosis, tuberculosis etc. Patient’s clinical details were obtained from the medical records.Results: The most frequent pathological finding was chronic salpingitis followed by salpingitis isthmica nodosa. It was noted that all cases with a positive history of pelvic inflammatory disease (PID), showed evidence of chronic salpingitis during histopathological examination. Chronic salpingitis was also noted in 45% cases who did not give a history of PID. Among the risk factors, a history of tubal sterilization was the most frequent one.Conclusions: Even though the mortality has reduced, ectopic pregnancy causes significant morbidity and affects the fertility of women. The rise in incidence could be due to increase in prevalence of sexually transmitted diseases, increase in tubal sterilization practices and frequent use of assisted reproduction technology. It is evident from the study that many cases of PIDs are left unidentified.

Heterotopic Pregnancy Secondary to in vitro Fertilization-Embryo Transfer: Risk Factors and Pregnancy Outcomes.

BackgroundWith the widespread application of assisted reproduction technology (ART) and increased pelvic inflammatory disease, the incidence of heterotopic pregnancy (HP) has risen. However, the risk factors and treatment of HP remain indefinite.ObjectivesTo explore risk factors affecting the incidence of HP secondary to in vitro fertilization-embryo transfer (IVF-ET) and pregnancy outcomes after surgical treatment of HP.Methods29 patients with HP and 116 with an intrauterine-only pregnancy (IUP) after IVF-ET during the same period were included retrospectively from January 2015 to September 2020.ResultsPatients with HP had a higher proportion of previous ectopic pregnancies, multiple abortion history (≧2 times) and tubal indication for IVF than IUP. Besides, they had a greater possibility to end in spontaneous abortion (31.03 vs.13.79%, P = 0.028) and preterm delivery (25.00 vs. 7.00%, P = 0.035), less possibility to result in a live birth (58.62 vs. 78.45%, P = 0.028). History of multiple abortions (≥2 times) [odds ratio (OR) 3.031, 95% confidence intervals (CI) 1.087–8.453; P = 0.034], tubal infertility (OR 3.844, 95% CI 1.268–11.656; P = 0.017), previous ectopic pregnancies (OR 2.303, 95% CI 0.625–8.490; P = 0.021) and number of embryo transfer (OR 0.300, 95% CI 0.092–0.983; P = 0.037) resulted in an elevated proportion of HP in IVF treatment. Shorter operative duration, smaller size of the ectopic mass and location in the ampulla of the fallopian tube were associated with higher chance of survival in the coexistent intrauterine pregnancy after surgical treatment.ConclusionsPrevious history of ectopic pregnancy, multiple abortions, tubal infertility and multiple-embryo transfer may be considered as meaningful risk factors of subsequent HP following IVF-ET. In patients with HP treated by surgery, shorter operative duration, smaller size of the ectopic mass and location in the ampulla of the fallopian tube means better reproductive prognosis.

In vitro fertilization cycle and embryo transfer outcomes in oligoanovulatory patients with hypothalamic hypogonadism vs. polycystic ovary syndrome and compared with normo-ovulatory patients

ObjectiveTo study the difference in the live birth rates between anovulatory women with hypothalamic hypogonadism (HH) and those with polycystic ovary syndrome (PCOS) and normo-ovulatory women undergoing fresh embryo transfer or frozen embryo transfer (FET).DesignRetrospective cohort study.SettingAcademic medical center.Patient(s)Patients with oligoanovulation (HH, n = 47; PCOS, n = 533) and normo-ovulation (tubal factor infertility, n = 399) undergoing in vitro fertilization and intracytoplasmic sperm injection cycles from January 1, 2012, to June 30, 2019.Intervention(s)None.Main Outcome Measure(s)Live birth rate.Result(s)Patients with HH had longer stimulation durations than both patients with PCOS and tubal factor infertility. Patients with HH had fewer oocytes retrieved than patients with PCOS, but their numbers of blastocysts were similar. Patients with HH and tubal factor infertility had similar numbers of oocytes retrieved and blastocysts. In fresh embryo transfer cycles, the live birth rates were similar among patients with HH, PCOS, and tubal factor infertility (37.5% vs. 37.1% vs. 29.3%, respectively). When evaluating FET cycles, patients with HH had lower live birth rates than patients with PCOS (26.5% vs. 46.7%) and tubal factor infertility (42.6%).Conclusion(s)Live birth rates are similar among patients with HH, PCOS, and normo-ovulation undergoing fresh embryo transfer but are significantly lower in women with HH undergoing FET.

Is There Still a Place for Reconstructive Surgery in Distal Tubal Disease?

Tubal diseases account for 25–40% of female factor infertility. Mainly, they involve the distal part of the fallopian tube, and hydrosalpinx is the most severe manifestation. Usually, the management decision is made between reconstructive surgery and ART, depending on the severity of the tubal damage, patient age, ovarian reserve, and seminogram, as well as financial, religious, ethical, and psychological factors. Estimated live-birth rates after corrective surgery range from 9% to 69%. The success rate of IVF is about 30% live-birth rate per cycle initiated in women across all ages with tubal factor infertility. Surgery offers a long-term cure and patients may attempt conception many times but are burdened with perioperative adverse events. IVF bypasses potential complications of operative treatment; however, this has its own unique risks. The effectiveness of reconstructive surgery versus ART has not been adequately evaluated. The success of fertility management depends on a thorough interpretation of existing data and careful patient selection. The presented review provides updates on the most recent progress in this area.

Subsequent left distal tubal pregnancy following laparoscopic tubal sterilization: a case report

Background: Post-sterilization pregnancies are rare and many postulations were made for its mechanism. Abdominal pain in women with retained uterus mandates a pregnancy test, regardless of previous tubal surgery or sterilization surgery to exclude the possibility of ectopic pregnancy. Prevention via surgical approach not only prevents future occurrence but also confer prophylaxis measure against ovarian cancer. Case: A 39-year-old woman who had undergone open right salpingectomy due to tubal pregnancy presented with abdominal pain, a positive pregnancy test, and elevated beta-human chorionic gonadotropin (β-hCG) level. Furthermore, an ultrasound exam revealed the absence of a gestational sac in the uterine cavity but the presence of a left adnexal mass; hence ectopic pregnancy was suspected. Laparoscopy revealed a 3 × 4 cm bulging ectopic pregnancy at the left distal end of the remnant stump in the ampulla. The histopathological assessment confirmed ectopic pregnancy in the left distal tubal stump. Post-operation, β-hCG levels decreased. The patient fully recovered postoperatively. Discussion: Ectopic pregnancies after tubal sterilization are caused by fistula formation and intraperitoneal sperm transmigration. To avoid this possibility, surgical techniques should be used to obliterate the residual canal, including the precise location and depth of electrocautery to prevent fistula formation. Total salpingectomy is the recommended treatment approach for effective permanent sterilization and a prophylaxis measure against ovarian cancer.

Assisted Reproductive Technology Treatment, the Catalyst to Amplify the Effect of Maternal Infertility on Preterm Birth.

ObjectiveTo identify the influence of different infertility causes and assisted reproductive technology (ART) treatment on perinatal outcomes and clarify the relationship between the maternal pathophysiological changes and artificial interventions.MethodsA total of 1,629 fertile women and 27,112 infertile women with sole infertility causes were prospectively recruited from July 2014 to December 2017, and 9,894 singletons were finally enrolled into the study. Pregnancies with more than one cause of infertility and/or multiple births were excluded. According to the causes of infertility and the exposure of ART treatment, the participants were divided into four groups, namely, fertile naturally conceived (NC) group, infertile NC group, female factor ART group, and male factor ART group. Perinatal outcomes, including gestational age of delivery (GA), birth weight (BW), preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA), and large for gestational age (LGA), were compared among groups. Logistic regression was performed for the adjustment of several covariates.Result(s)The birth outcomes of the infertile NC group and fertile NC group, female factor ART group, and infertile NC group were comparable. Compared to the fertile NC group, the female factor ART group had a shorter GA (39.0 ± 1.6 vs. 39.3 ± 1.5 weeks, BW: P < 0.05). An interaction test showed that ART treatment had an interaction on the effect of female infertility on GA (P = 0.023). The female factor ART group also had a higher risk of PTB (OR 1.56, 95% CI 1.18–2.07) and LGA (OR 1.27, 95% CI 1.10–1.47) compared to the fertile NC group. The risk of PTB was increased for tubal factor ART (OR 1.49, 95% CI 1.12–2.00), ovulatory dysfunction ART (OR 1.87, 95% CI 1.29–2.72), and unexplained infertility ART (OR 1.88, 95% CI 1.11–3.17). The risk of LGA was increased for tubal factor ART (OR 1.28, 95% CI 1.11–1.48) and ovulatory dysfunction ART (OR 1.27, 95% CI 1.03–1.57).Conclusion(s)Our findings indicated that ART treatment could amplify the adverse effect of female infertility on neonates. Women with tubal factor infertility, ovulatory dysfunction, and unexplained infertility have a higher risk of PTB after ART treatment. Thus, clinicians should be vigilant in such patients and provide corresponding prevention strategies before and during pregnancy.

A New Methodology to Assess Fallopian Tubes Microbiota and Its Impact on Female Fertility

Tubal factor is an important contributor to female infertility, and the current diagnostic approaches cannot correctly identify many subtle causes of tubal dysfunction. While it is known that the most common cause of tubal factor infertility is pelvic inflammatory disease (PID), creating critical alterations of the tubal epithelium, little attention has been devoted to understanding the tubal modifications caused by the resident microbial population and their interaction with the surrounding tubal epithelium. Furthermore, most of these samples are obtained by traumatic procedures such as direct sampling during laparoscopy using a cytobrush. However, as in any other organ of the female genital tract, the microbiota environment of the fallopian tube plays an essential role in maintaining tubal functioning, counteracting the pathogenic effect of acquired microbes. Consequentially, to better analyze the tubal microbiota without causing anatomical and/or functional alteration of the fallopian tube and preserving fertility, the hysteroscopic approach might be the method of choice, guarantying maximal integrity of the uterine cavity and tubal lumen. Here we describe our plan for using atraumatic hysteroscopic sampling methods to investigate the correlation between tubal microbiota and female infertility.

Systemic vascular resistance may influence the outcome of in vitro fertilization

Introduction: The number of pregnancies obtained through in vitro fertilization (IVF) techniques are increasing, and only few studies have investigated hemodynamic variations in women undergoing IVF techniques. The aim of this study was to evaluate the hemodynamic parameters in women undergoing IVF, to assess a possible correlation between hemodynamics and embryo implantation. Methods: 45 normotensive non-obese women, age ≤ 43 years, with idiopathic or tubal infertility, referred to the Reproductive Physiopathology and Andrology Unit, Sandro Pertini Hospital, Rome, during the period 2020/2021, underwent IVF techniques. All women were evaluated with Ultra Sonic Cardiac Output Monitor (USCOM) to detect hemodynamic parameters at two different stages: at the mid-luteal phase, before the beginning of IVF, and at the day of embryo transfer (dET). All demographics and hormonal parameters in both groups were comparable. The hemodynamic parameters were compared between women with a positive β-HCG test vs. those testing negative. Results: 11 out of 45 (24,5%) women obtained positive β-HCG test. All demographics and hormonal parameters were comparable in both groups. Women with a positive β-HCG test showed statistically lower systemic vascular resistance (SVR) at mid-luteal phase (868.61 ± 100.1 vs. 1009 ± 168.4) and dET (818,9 ± 104.5 vs 1038.52 ± 150.82 dynes × s/cm5). Conclusions: Hemodynamic assessment can identify a more favorable pre-pregnancy cardiovascular adaptation. Embryo implantation might be positively influenced by the hemodynamic parameters, e.g. lower SVR, before the beginning of IVF techniques, and during the window of implantation.

Evaluation of monocyte chemotactic protein-1 level in serum of fertile and infertile women

Infertility is a disease of the reproductive system characterized by inability to achieve pregnancy after 12 or more months of regular unprotected sexual intercourse (Venkatesh et al., 2014). Female infertility, as a complex disorder, may be caused by medical conditions including pelvic inflammatory disease, endometriosis related infertility, ovulatory disorders, tubal factor infertility, and unexplained infertility(Gupta et al., 2014). Infertility affect approximately nine to fifteen percent of the childbearing population, and 55% of these influenced will seek medical help to achieve their desire to have children (Boivin et al., 2011).

Ascending Reproductive Tract Infection in Pig-Tailed Macaques Inoculated with Mycoplasma genitalium.

ABSTRACTMycoplasma genitalium is a sexually transmitted bacterial pathogen that causes urogenital disease in men and women. M. genitalium infections can persist for months to years and can ascend to the upper reproductive tract in women where it is associated with serious sequelae including pelvic inflammatory disease, tubal factor infertility, and preterm birth. An animal model is needed to understand immune evasion strategies that allow persistence, mechanisms of ascending infection, and factors associated with clearance. In earlier studies, we determined that pig-tailed macaques are susceptible to cervical infection; however, not all primates were successfully infected, persistence varied between animals, and ascension to the upper reproductive tract was not observed after 4 or 8 weeks of follow-up. Building on our previous findings, we refined our inoculation methods to increase infection rates, extended observation to 18 weeks, and comprehensively sampled the upper reproductive tract to detect ascending infection. With these improvements, we established infection in all (3/3) primates inoculated with M. genitalium and demonstrated lower tract persistence for 16 to 18 weeks. Ascension to the upper reproductive tract at endpoint was observed in two out of three primates. All three primates developed serum and local antibodies reacting primarily to the MgpB and MgpC adherence proteins. Elevated genital polymorphonuclear leukocytes (PMNs) and inflammatory cytokines and chemokines, erythema of the ectocervix in one primate, and histologic evidence of vaginitis and endocervicitis in two primates suggest a mild to moderate inflammatory response to infection. This model will be valuable to understand the natural history of M. genitalium infection including mechanisms of persistence, immune evasion, and ascension to the upper reproductive tract.

The Correlation between Chlamydia Trachomatis and Female Infertility: A Systematic Review.

The impact of Chlamydia trachomatis (CT) infection on female's fertility is not completely established yet, since the level of evidence associating these factors is still weak. Hence, the goal of the present review is to contribute to a better elucidation of this matter. The electronic database chosen was the Medline/PubMed, with the last survey on May 11, 2021. Publication date was used as a filter, with the previous 5 years having been selected. The following describers were used: chlamydia trachomatis AND infertility; chlamydia trachomatis AND tubal alteration AND infertility; chlamydia AND low pregnancy rates. From the 322 studies screened, 293 that failed to meet our eligibility criteria were excluded. Subsequently, we removed seven studies for not having the possible correlation between CT infections and female infertility as its main focus, and three for being about sexually transmitted infections (STIs) in general. Moreover, two studies designed as reviews were also excluded. Ergo, we included 17 studies in our qualitative analysis. The authors conducted research individually and analyzed carefully the studies selected. As we retrieved the information needed for our study through reading the texts, no contact was made with the authors of the studies selected. This systematic review corroborates the hypothesis that CT infection potentiates female infertility, as 76.47% of the included studies found a positive correlation between them. We conclude that there is an important association between CT infection and female infertility. Ergo, making CT screening part of the infertility investigation routine is relevant and has a reasonable justification.

Top-quality embryo transfer is associated with lower odds of ectopic pregnancy.

The incidence of ectopic pregnancy is up to four times higher after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) than in spontaneous pregnancies, and the risk of ectopic pregnancy is increased by tubal factor infertility and the transfer of multiple embryos. However, the effect of embryo quality on the probability of ectopic pregnancy has not been investigated until now and it is not clear whether ovarian stimulation parameters affect the incidence of ectopic pregnancy. An historical cohort study of 15 006 clinical pregnancies (diagnosed by ultrasound at 6-8gestational weeks) after non-donor IVF/ICSI with fresh embryo transfer (n=8952) or frozen-thawed embryo transfer (n=6054). Treatments were performed during 2000-2017 in Finland. A total of 9207 (61.4%) single and 5799 (38.6%) double embryo transfers of no more than one top-quality embryo were evaluated. We analyzed the effects of multiple factors on ectopic pregnancy by logistic regression, including type of cycle (fresh vs frozen embryo transfer), female age, number and quality of embryos transferred, tubal factor infertility and factors of ovarian response to gonadotropin stimulation. Ectopic pregnancy was observed in 2.3% of cycles. There was no significant difference in ectopic pregnancy rate after fresh embryo transfer and frozen embryo transfer (2.2% vs 2.4%, p=0.3). The ectopic pregnancy rate was lower in cycles with top-quality embryo transfer (1.9%) than of those where only non-top quality embryos were transferred (2.7%, p < 0.0001). Tubal factor infertility was diagnosed more often in ectopic pregnancy than in intrauterine pregnancies (21.2% vs 11.0%, p < 0.0001). Logistic regression revealed lower odds for ectopic pregnancy after a top-quality embryo transfer than after transfer of a non-top quality embryo (odds ratio [OR] 0.72, 95% confidence interval [CI] 0.56-0.92, p=0.007). Transfer of two vs one embryo (OR 1.35, 95% CI 1.05-1.70, p=0.02) and tubal factor infertility (OR 2.21, 95% CI 1.68-2.91, p < 0.0001) significantly increased the risk of ectopic pregnancy. Transfer of non-top quality embryos is associated with a higher rate of ectopic pregnancy. This is particularly important to keep in mind in treatments with only non-top embryos available even in the absence of tubal factor infertility. To minimize the risk of ectopic pregnancy, the number of embryos transferred should be as low as possible.

Short-notice cancellations of laparoscopic permanent contraception

ObjectivePermanent contraception through tubal sterilization is the preferred contraceptive method for 25% of women in the United States. Laparoscopic permanent contraception has an anecdotally high cancellation rate. Cancellations affect operating room utilization and may reflect barriers to care. We aimed to identify the short-notice cancellation (≤7 days from scheduled surgery) rate for laparoscopic permanent contraception, reasons for cancellation, and postcancellation outcomes. Study DesignWe performed a retrospective chart review of patients aged 18 to 50 who canceled or no-showed a scheduled laparoscopic permanent contraception surgery between May 2016 and May 2019 at an academic tertiary care hospital and academic county hospital in Denver, Colorado. We reviewed electronic health records to determine the time between cancellation and surgery date and documented reasons for cancellation. We evaluated contraceptive methods used and pregnancies within a year after the canceled surgery. ResultsThe overall surgery cancellation rate for scheduled laparoscopic permanent contraception was 22% (123 of 558). Short-notice cancellation occurred for 71.5% of patients and 32.5% (40 of 123) canceled same day. The most common reason for cancellation was patient choice (74%) followed by financial/insurance issues (11.4%). In the year after their canceled surgery, 22% (27 of 123) of patients obtained permanent contraception and 5.7% (7 of 123) had a subsequent pregnancy. ConclusionsAmong patients who canceled their laparoscopic permanent contraception, the vast majority canceled their surgery a week or less from their scheduled date. These short-notice cancellations may adversely affect both patients and the health care system. More research is needed on institutional policies to reduce laparoscopic permanent contraception cancellations while helping patients who want effective contraception find an option that works best for them. ImplicationsOur retrospective cohort study found that laparoscopic permanent contraception surgeries have an overall high cancellation rate at both an academic tertiary and an academic county hospital, with most cancellations occurring less than 7 days prior to surgery. Future research will be used to reduce barriers to permanent contraception while developing clinical tools to reduce surgery cancellation rates.

Bisphenol A correlates with fewer retrieved oocytes in women with tubal factor infertility

Serum and urinary bisphenol A (BPA) concentrations have been associated negatively with the number of retrieved oocytes after in vitro fertilization (IVF). The impact of BPA upon women with polycystic ovary syndrome (PCOS) and women with tubal factor infertility (TFI), following IVF, was investigated. To this purpose, associations among serum and urinary and follicular fluid (FF) BPA concentrations and the number of retrieved and fertilized oocytes and comparisons between pregnancy rates were evaluated. This was a cross-sectional study conducted at a university-affiliated assisted conception unit between January and November 2019, including 93 women of reproductive age (PCOS: 45; TFI: 48) following IVF. Unconjugated FF and serum BPA concentrations and total urinary BPA concentration were measured using a novel gas chromatography-mass spectrometry method. The number of retrieved and fertilized oocytes and pregnancy rate were documented and evaluated. The number of oocytes retrieved from PCOS women was greater than that of 21 TFI women, independently of BMI. Lower FF BPA concentrations were found in all PCOS women and in overweight/obese PCOS compared to TFI women (0.50, 0.38, and 1.13ng/mL, respectively). In TFI women, FF BPA concentrations correlated negatively with the number of retrieved oocytes. Serum and FF and urinary BPA concentrations did not significantly affect the number of fertilized oocytes and pregnancy rate in both groups. FF BPA concentrations were lower in all PCOS women and in overweight/obese PCOS than in TFI women. In TFI women, FF BPA concentrations correlated negatively with retrieved oocytes. Confirmation of these findings might lead to moderation of use of BPA-containing products by women undergoing IVF.

Evaluation of a Multiplex Real-Time PCR Assay for Detecting Chlamydia trachomatis in Vaginal Samples.

Chlamydia trachomatis is an important cause of sexually transmitted infections (STI) in Western countries. It is often asymptomatic, and thus, left untreated, and can have severe negative consequences, such as tubal infertility or adverse pregnancy outcomes. Other sexually transmitted microorganisms, such as Neisseria gonorrhoeae and Trichomonas vaginalis, as well as normal residents of the vaginal flora, such as genital mycoplasmas, also negatively impact human sexual and reproductive health. We evaluated the reliability of the Seegene Allplex STI Essential Assay for C. trachomatis detection using the real-time qPCR routinely used in our diagnostic laboratories as the gold standard. The Seegene assay displayed a sensitivity of 97.8% and a specificity of 98.9%. As this assay can also detect six other urogenital pathogens, we applied it to 404 samples from women who attended Lausanne University Maternity Hospital and obtained the following prevalence rates: 2.5% for C. trachomatis, 3.5% for Mycoplasma hominis, 6.3% for Ureaplasma urealyticum, and 27.7% for Ureaplasma parvum. Two samples were positive for Trichomonas vaginalis, and one sample was positive for Mycoplasma genitalium. Bacterial vaginosis was present in 4.5% of the cases and was strongly associated with M. hominis. Finally, we confirmed the association between C. trachomatis infection and pre-term birth (p = 0.03) but could not detect any association of this condition with other urogenital pathogens (Mycoplasma/Ureaplasma). In conclusion, given its high sensitivity and specificity for C. trachomatis DNA detection as well as its multiplex format, which simultaneously provides results for six other urogenital pathogens, the Seegene Allplex™ STI Essential Assay represents an appealing diagnostic tool in modern microbiology laboratories.