Clinical relevance of a newly developed endometrial receptivity test for patients with recurrent implantation failure in Japan.

Purpose: To assess the clinical efficacy of personalized embryo transfer (pET) guided by a new endometrial receptivity test, ERPeakSM, in patients with recurrent implantation failure (RIF). Methods: Recurrent implantation failure patients of all ages at two private Japanese clinics from April 2019 to June 2020 were retrospectively analyzed. The intervention group (n = 244) received pET in accordance with endometrial receptivity testing results and was compared to control group (n = 306) receiving standardized timing, non-personalized embryo transfer (npET). In propensity score matching analysis, the clinical pregnancy rate (CPR) and live birth rate (LBR) were compared between groups, and a subanalysis of advanced maternal age (AMA) (≥38 years old) versus non-AMA (<38 years old) patients was also conducted. Results: The CPR and LBR of the pET group were significantly higher than those of the npET group (37.7% vs. 20.0%, adjusted OR: 2.64; 95%CI, 1.70-4.11, p < 0.001 and 29.9% vs. 9.7%, adjusted OR: 4.13; 95%CI, 2.40-7.13, p < 0.001, respectively). Furthermore, in the subanalyses, the CPR and LBR of the pET group were significantly higher than those of the npET group in both the AMA non-AMA patients. Conclusions: The new ERPeakSM endometrial receptivity test is a useful alternative diagnostic tool for poor-prognosis patients, regardless of age.

Chromosomal copy number analysis of products of conception by conventional karyotyping and next-generation sequencing.

PURPOSE: Chromosomal abnormalities are a major cause of spontaneous abortion, and conventional G-banded karyotyping (G-banding) is mainly utilized for chromosomal analysis. Recently, next-generation sequencing (NGS) has been introduced for chromosomal analysis. Here, we aimed to investigate the applicability and utility of NGS-based chromosomal analysis of products of conception (POC) on chorionic villus samples from spontaneous abortion. METHODS: The results of chromosomal analysis of 7 chorionic villus samples from spontaneous abortion were compared between conventional G-banding and NGS-based chromosomal copy number analysis. Age dependency and frequency of each chromosomal aneuploidy were evaluated for 279 cases analyzed by NGS. RESULTS: Excluding two cases (culture failure and maternal cell contamination), the results were consistent between G-banding and NGS. For cases analyzed by NGS, the rate of chromosomal abnormality increased in a maternal age-dependent manner. The frequency of each chromosomal aneuploidy detected by NGS was almost the same as that previously reported. Finally, NGS analysis was possible for difficult cases by G-banding analysis, such as culture failure, maternal cell contamination, long-term storage cases, and low cell number. CONCLUSIONS: Chromosome analysis using NGS not only obtains comparable results to conventional G-banding, but also can analyze POC more accurately and efficiently.

Clinical background affecting pregnancy outcome following local endometrial injury in infertile patients with repeated implantation failure.

Local endometrial injury (LEI) has been performed as a promising medical intervention to improve the pregnancy outcome in infertile women suffering from repeated implantation failure (RIF) in in vitro fertilization-embryo transfer cycles. The effect of LEI, however, remains controversial. The aim of this retrospective study was to identify the subgroups of patients with RIF who benefit from LEI. We compared the clinical parameters between the patients who had had a clinical pregnancy in the subsequent embryo transfer cycle following the LEI cycle (LEI-CP group, n = 94) and those who had resulted in negative pregnancy test (LEI-NP group, n = 114). The female age, basal follicle stimulating hormone concentration, number of past oocyte pickup cycles, and embryos/blastocysts transferred in the past three RIF cycles were significantly (p < 0.047) lower in the LEI-CP group than the LEI-NP group. The prevalence of polycystic ovarian syndrome was significantly (p = 0.0059) higher in the LEI-CP group than in the LEI-NP group. These findings suggest that LEI is most effective to improve the pregnancy outcome in patients undergoing RIF with uncompromised ovarian reserve, particularly in those with polycystic ovarian syndrome.

Falloposcopic tuboplasty: an easy, quick, and safe technique.

OBJECTIVE: To describe our simplified technique for falloposcopic tuboplasty (FT) and demonstrate its principle and results. DESIGN: A step-by-step description of the technique and demonstration of its principle using a clay model. SETTING: Private infertility clinics in Osaka and Tokyo operated by 10 physicians. PATIENT(S): A total of 431 infertile women with a diagnosis of unilateral or bilateral proximal tubal occlusion (6 cm from the uterotubal ostia), between October 2013 and February 2019 were included. These patients underwent routine work-ups for infertility, including a semen analysis, hysterosalpingography, antimüllerian hormone, basal luteinizing hormone/follicle-stimulating hormone and prolactin concentrations during menstruation, postcoital test in the periovulatory period, and estradiol and progesterone concentrations in the middle of the luteal phase. Physicians performed hysterosalpingography to evaluate tubal patency and uterine shape. Saline infusion sonography was not conducted because it does not accurately identify regions of tubal occlusion and/or stenosis. INTERVENTION(S): The principle of our simplified technique for FT is that a hole is located at the side of the FT catheter tip. Therefore, the balloon and fiberscope move away from the catheter line (Fig. 1). The uterotubal ostium is located at the tip-end of the triangle of the uterine cavity. When a balloon is inserted while visualizing the uterotubal ostium at the nearest position to the ostium, the balloon hits the uterine wall. When a balloon is inserted 5-10 mm from the uterotubal ostium without visualization, the balloon may be easily placed in the ostium through its convex angle, allowing it to slide into the uterine wall (Figs. 2 and 3). Step 1: Confirm anteflexion or retroflexion of the uterus by ultrasound. Step 2: Confirm the direction of the uterotubal ostia by hysteroscopy. Step 3: Adjust the angle of the FT catheter according to steps 1 and 2, insert the catheter into the end of the uterus, pull it back 5-10 mm (without visualizing the uterotubal ostia), and then fix it to the forceps. Catheter placement away from the tubal ostium is confirmed by the residual length of the moving part of the catheter. An attending instructor should ask the operator about the feeling of rigidity when the catheter does not advance and then suggest whether to proceed or stop. In the latter case, the catheter is not moved, saline is infused for 1 minute for lubrication, the balloon is pulled back using the fiberscope to remove the bunching of the balloon, and balloon pressure is changed as follows: 6→8→6→10→6 mmHg. Our institutional review board stated that approval was not required because the video describes the technique of our routine procedure. MAIN OUTCOME MEASURE(S): A description of the FT technique using a clay model and a demonstration of its application in our clinic. RESULT(S): The average operative time was 15.4 minutes, and the clinical pregnancy rate was 24.4% (natural conception and intrauterine insemination without in vitro fertilization). No significant differences were observed in the operative time or pregnancy rate among physicians. Approximately 17 FT procedures may be performed using one fiberscope. CONCLUSION(S): Our simplified technique, which was described and demonstrated in this video article, is a feasible and practical approach for performing FT. It provides excellent cost performance by saving fiberscopes. The most important point is "Introduce the balloon and fiberscope 5-10 mm away from the uterotubal ostia without visualizing it." To facilitate learning this technique, we recommend watching the video and then practicing FT without searching for the uterotubal ostia. Physicians master FT without any assistance by an attending instructor in ≤3 attempts.

Minimum values for midluteal plasma progesterone and estradiol concentrations in patients who achieved pregnancy with timed intercourse or intrauterine insemination without a human menopausal gonadotropin.

OBJECTIVE: The aim of the study was to assess the lower limits of midluteal plasma progesterone and estradiol concentrations in patients who achieved pregnancy with timed intercourse or intrauterine insemination without a human menopausal gonadotropin stimulation. RESULTS: We included 297 pregnant cycles of 297 women and assessed midluteal plasma progesterone and estradiol concentrations and pregnancy outcomes, retrospectively. These cycles were compared with the non-pregnant cycles (406 cycles) of the same women who became pregnant. Mean midluteal plasma P4 and E2 concentrations were significantly (P < 0.01) higher in pregnant cycles (14.5 and 188.5 pg/mL) than in non-pregnant cycles (10.7 and 162.6 pg/mL). The 5 percentiles of progesterone and estradiol in pregnant cycles were 5.6 and 70.2 pg/mL, respectively. The lowest progesterone and estradiol levels in pregnant cycles were 2.3 and 23.4 pg/mL, respectively. In non-pregnant cycles, many women had low P4 levels that were less than 5.6 ng/mL. Subgroup analyses showed slight differences among the four groups, which may have been due to the ovarian function of each group. Miscarriage was not related to progesterone and estradiol concentrations. These values may be useful for the evaluation of necessary values for pregnancy with timed intercourse or intrauterine insemination.

Is a high serum copper concentration a risk factor for implantation failure?

BACKGROUND: Copper-containing contraceptive devices may deposit copper ions in the endometrium, resulting in implantation failure. The deposition of copper ions in many organs has been reported in patients with untreated Wilson's disease. Since these patients sometimes exhibit subfertility and/or early pregnancy loss, copper ions were also considered to accumulate in the uterine endometrium. Wilson's disease patients treated with zinc successfully delivered babies because zinc interfered with the absorption of copper from the gastrointestinal tract. These findings led to the hypothesis that infertile patients with high serum copper concentrations may have implantation failure due to the excess accumulation of copper ions. The relationship between implantation (pregnancy) rates and serum copper concentrations has not yet been examined. The Japanese government recently stated that actual copper intake was higher among Japanese than needed. Therefore, the aim of the present study was to investigate whether serum copper concentrations are related to the implantation (pregnancy) rates of human embryos in vivo. METHODS: We included 269 patients (age <40 years old) who underwent vitrifying and warming single embryo transfer with a hormone replacement cycle using good blastocysts (3BB or more with Gardner's classification). Serum hCG, copper, and zinc concentrations were measured 16 days after the first date of progesterone replacement. We compared 96 women who were pregnant without miscarriage at 10 weeks of gestation (group P) and 173 women who were not pregnant (group NP). RESULTS: No significant differences were observed in age or BMI between the groups. Copper concentrations were significantly higher in group NP (average 193.2 µg/dL) than in group P (average 178.1 µg/dL). According to the area under the curve (AUC) on the receiver operating characteristic curve for the prediction of clinical pregnancy rates, the Cu/Zn ratio (AUC 0.64, 95% CI 0.54-0.71) was a better predictor than copper or zinc. When we set the cut-off as 1.59/1.60 for the Cu/Zn ratio, sensitivity, specificity, the positive predictive value, and negative predictive value were 0.98, 0.29, 0.71, and 0.88, respectively. CONCLUSIONS: Our single-center retrospective study suggests that high serum copper concentrations (high Cu/Zn ratio) are a risk factor for implantation failure.

Live birth rate following oral antibiotic treatment for chronic endometritis in infertile women with repeated implantation failure.

PROBLEM: The aim of this prospective study was to investigate the prevalence of chronic endometritis (CE) in infertile women with a history of repeated implantation failure (RIF) and to determine whether oral antibiotic treatment improves their live birth rate in the following embryo transfer (ET) cycles. METHOD OF STUDY: Endometrial biopsy samples obtained from infertile women with RIF were subjected to immunohistochemistrical/histopathologic diagnosis of CE. Following antibiotic administration to the RIF/CE group, their histopathologic cure rate, microbial detection rate, and reproductive outcome in the subsequent ET cycles were prospectively studied. RESULTS: 33.7% of infertile women with RIF were diagnosed with CE. Following the first-line doxycycline treatment, the histopathologic cure rate in the subsequent endometrial biopsy was 92.3%. Following the second-line metronidazole/ciprofloxacin treatment, the overall cure rate was 99.1%. The live birth rate in the first ET cycle (P=.031, RR 1.48, 95% CI 1.03-2.12) and cumulative three ET cycles (P=.037, RR 1.39, 95% CI 1.02-1.90) following antibiotic treatment in the cured RIF/CE group (32.8% and 38.8%, respectively) was significantly higher than in the RIF/non-CE group (22.1% and 27.9%, respectively). CONCLUSION: Chronic endometritis was found in one-third of infertile women with RIF. The oral antibiotic treatment against CE might be a promising therapeutic option for infertile women with RIF.

Chronic Endometritis: Potential Cause of Infertility and Obstetric and Neonatal Complications.

Chronic endometritis (CE) is a local inflammatory disease characterized by unusual plasmacyte infiltration in the endometrial stromal areas. CE has been neglected in gynecologic practice, as it is a less symptomatic benign disease that requires demanding and time-consuming histopathologic examinations for the definite diagnosis. Recent studies, however, suggest the association of CE with infertility and obstetric and neonatal complications. In this review article, we aimed to update the knowledge on epidemiology, etiology, and pathogenesis of CE as well as discuss its clinical management from diagnosis to treatment.

Peritonitis caused by a ruptured, infected mesenteric cyst initially interpreted as an ovarian cyst. A case report.

BACKGROUND: Mesenteric cysts are rare intraabdominal lesions of childhood that may vary in presentation from an asymptomatic mass to an acute abdomen. CASE: We encountered a rare case of peritonitis caused by a ruptured, infected mesenteric cyst of the mesocolon in a female child that had been initially interpreted as a ruptured ovarian cyst. CONCLUSION: When confronted with a large unilocular or septated echolucent mass in the lower abdomen in female children, gynecologists should consider a mesenteric cyst in the differential diagnosis.