A Prospective Cohort Study of Metformin as an Adjuvant Therapy for Infertile Women With Endometrial Complex Hyperplasia/Complex Atypical Hyperplasia and Their Subsequent Assisted Reproductive Technology Outcomes.

Objective: To investigate the adjuvant efficacy of metformin treatment to achieve pathological complete response (CR) in patients with endometrial complex hyperplasia (CH) and complex atypical hyperplasia (CAH), and secondarily, to evaluate their pregnancy outcomes after following assisted reproductive technology (ART). Study Design: This prospective cohort study analyzed 219 patients diagnosed with infertility and CH/CAH from January 2016 to December 2020. Among these patients, 138 were assigned to the control group (progesterone alone) and 81 were assigned to the study group (progesterone+metformin). After 8/12 weeks of therapy, the treatment responses were assessed by histological examination of curettage specimens obtained by hysteroscopy. Once the pathological results indicated CR, the patients were able to receive ART. The ART treatment and follow-up data of these patients were collected and analyzed. Results: 116 patients in the control group achieved CR, compared with 76 patients in the study group. The CR rate in the control group was significantly lower than that in the study group (P=0.034). We then divided the patients into subgroups to compare the treatment responses. In the subgroup analyses, patients with body mass index (BMI) ≥25 kg/m2 and patients with polycystic ovarian syndrome (PCOS) had higher CR rates in the metformin group compared with the control group (P=0.015, P=0.028 respectively). Subsequently, 68 patients in the control group and 47 patients in the study group received an ART cycle. We examined the pregnancy indications and found no significant differences in the clinical pregnancy rate and live birth rate between the two groups (P>0.05). Conclusion: Regression of CH/CAH may be improved by progesterone+metformin compared with progesterone alone. The effect was particularly pronounced in patients with BMI ≥25 kg/m2 and patients with PCOS. Metformin had no obvious effect on subsequent ART outcomes. The trial is registered on the publicly accessible website. Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=15372, identifier ChiCTR-ONR-16009078.

Effects of bicornuate uterus on pregnancy and obstetric outcomes of in vitro fertilization / intracytoplasmic sperm injection.

OBJECTIVE: A bicornuate uterus results from failure of the Müllerian ducts to completely fuse. If patients with bicornuate uterus are diagnosed with infertility, they can conceive with help from in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). With few studies on the reproductive performances of bicornuate uterus following IVF/ICSI treatment, the aim of present study is to investigate whether a bicornuate uterus would affect pregnancy rates and obstetric outcomes of infertile women. STUDY DESIGN: A retrospective cohort study contained 232 women (58 with bicornuate uterus and 174 with normal uterus) was conducted. Patient data for IVF/ICSI treatment and follow-up were collected and analyzed. Cumulative pregnancy rate and cumulative live birth rate after one complete assisted reproductive technology (ART) cycle were the primary outcomes. RESULTS: Baseline characteristics were comparable between the bicornuate uterus group and the control group. Ovarian response to stimulation and embryological results were similar between the two groups. In fresh embryo transfer cycles, embryo implantation rate (32.7 % vs. 42.9 %, P = 0.176), biochemical pregnancy rate (54.1 % vs. 64.9 %, P = 0.236), and clinical pregnancy rate (45.9 % vs. 58.8 %, P = 0.172) did not differ significantly between the bicornuate uterus group and the control group. Live birth rate (40.5 % vs. 43.9 %, P = 0.723), term delivery rate (93.3 % vs. 90.0 %, P = 0.696), cesarean section rate (73.3 % vs. 76.0 %, P = 0.833), and newborn birth weight (3.35 ± 0.56 vs. 3.32 ± 0.51, P = 0.524) also did not differ significantly between the two groups. In frozen-thawed embryo transfer cycles, there were no significant differences in outcomes between the two groups. Upon completion of one IVF/ICSI cycle, cumulative pregnancy rate (59.6 % vs. 71.0 %, P = 0.112) and cumulative live birth rate (58.2 % vs. 64.8 %, P = 0.375) were similar between the two groups. CONCLUSION: There were no significant differences in ovarian responses, pregnancy outcomes, and obstetric outcomes after IVF/ICSI treatment between women with bicornuate uterus and women with normal uterus. Bicornuate uterus had no significant negative effects on cumulative IVF/ICSI outcomes of infertile patients.

Does a hyperechogenic endometrial mass in the uterus during controlled ovarian stimulation affect assisted reproductive technology cycle outcomes?

OBJECTIVES: Healthy embryos and endometrial receptivity are keys to the success of in-vitro fertilization and embryo transfer (IVF-ET). Abnormal transvaginal ultrasonography (TVU) findings in the endometrium are a concern during assisted reproductive technology (ART) treatments. Observation of a hyperechogenic endometrial mass (HEM) during controlled ovarian stimulation (COS) in an IVF or intracytoplasmic sperm injection (ICSI) cycle is a dilemma. Here we investigated whether an HEM would affect ART cycle outcomes. STUDY DESIGN: We analyzed all data from patients who underwent IVF or ICSI treatment cycles from January 1, 2009 to December 31, 2016 at our institution. Patients diagnosed with an HEM were included. Each woman was matched with two control subjects of similar age (± 1 year), in terms of the number of cycles, type of infertility (primary or secondary), protocol used for COS, but with no HEM identified by TVU. Baseline characteristics, COS response, and pregnancy outcomes after ET were compared. RESULTS: In all, 1088 patients were diagnosed with an HEM. Of these, 426 met the inclusion criteria and were matched with 852 controls. Baseline characteristics showed no significant differences between the groups. The peak endometrial thickness was significantly greater in the experimental group than in the control group (1.15 ± 0.18 cm vs. 1.08 ± 0.21 cm, p < 0.001). The live birth rates were 43.7% vs 46.2% in the experimental and control groups, respectively. There were no significant between-group differences in the rates of biochemical or clinical pregnancy or abortions at any stage. CONCLUSIONS: Newly diagnosed HEMs < 18 mm in diameter monitored by TVU did not impair the outcomes of ART following COS in this study. If other conditions are suitable, completion of ART cycles should be the appropriate approach in such cases. KEY MESSAGE: Newly diagnosed hyperechogenic endometrial masses measuring <18 mm in diameter monitored by TVU during COS did not adversely affect the outcomes of these IVF/ICSI-ET cycles.

Optimal waiting period for fresh embryo transfer after hysteroscopic adhesiolysis: a retrospective cohort study.

BACKGROUND: Very few studies have been conducted regarding the optimal time interval between hysteroscopic adhesiolysis and the embryo transfer (ET). Investigation of this optimal time may be helpful for assisted reproductive technology. Therefore, we investigated effects of the interval between hysteroscopic adhesiolysis and ET upon in vitro fertilization (IVF) cycle outcomes. METHODS: Patients were recruited between January 2014 and September 2017 at the Reproductive Hospital Affiliated to Shandong University. Patients who were diagnosed with intra-uterine adhesion (IUA) and underwent hysteroscopic adhesiolysis before fresh IVF-ET or intra-cytoplasmic sperm injection cycles were classified into three groups according to the interval between hysteroscopic adhesiolysis and ET: less than 90 days (Group 1), 90 to 180 days (Group 2), and greater than 180 days (Group 3). Baseline characteristics, controlled ovarian stimulation (COS) response, and pregnancy outcomes after ET were compared. Analysis of variance or non-parametric tests were used to test numerical data. The Pearson's Chi-squared test was used to test categorical data. RESULTS: A total of 312 patients were recruited as follows: 112 in Group 1, 137 in Group 2, and 63 in Group 3. There were no differences in baseline and COS characteristics among the three groups. The live-birth rate in Group 2 (40.1%) was significantly higher than that in Group 1 (17.9%; χ = 14.545, P < 0.001). There were no significant differences in the rates of biochemical, ongoing, and clinical pregnancy, and biochemical and clinical pregnancy abortion, as well as stillbirth among the groups. In the mild IUA patients, the live-birth rate was significantly higher in Group 2 (42.6%) compared with Group 1 (22%; χ = 8.413, P = 0.004). In the moderate IUA patients, Group 2 (35.7%) had a higher frequency of live births than Group 1 (6.7%; χ = 8.187, P = 0.004). CONCLUSIONS: The optimal waiting period for fresh ET after hysteroscopic adhesiolysis was 90 to 180 days in the current study.