Therapeutic intervention based on gene sequencing analysis of microbial 16S ribosomal RNA of the intrauterine microbiome improves pregnancy outcomes in IVF patients: a prospective cohort study.

PURPOSE: A Lactobacillus-dominated microbiota in the endometrium was reported to be associated with favorable reproductive outcomes. We investigated in this study whether 16S ribosomal RNA (rRNA) gene sequencing analysis of the uterine microbiome improves pregnancy outcomes. METHODS: This prospective cohort study recruited a total of 195 women with recurrent implantation failure (RIF) between March 2019 and April 2021 in our fertility center. Analysis of the endometrial microbiota by 16S rRNA gene sequencing was suggested for all patients who had three or more failed embryo transfers (ETs). One hundred and thirty-one patients underwent microbial 16S rRNA gene sequencing (study group) before additional transfers, while 64 patients proceeded to ET without that analysis (control group). The primary outcome was to compare the cumulative clinical pregnancy rate of two additional ETs. MAIN RESULTS: An endometrial microbiota considered abnormal was detected in 30 patients (22.9%). All but one of these 30 patients received antibiotics according to the bacterial genus detected in their sample, followed by treatment with probiotics. As a result, the cumulative clinical pregnancy rate (study group: 64.5% vs. control group: 33.3%, p = 0.005) and the ongoing pregnancy rate (study group: 48.9% vs. control group: 32.8%, p = 0.028) were significantly increased in the study group compared to the control group. CONCLUSION: Personalized treatment recommendations based on the microbial 16S rRNA gene sequencing of the uterine microbiota can improve IVF outcomes of patients with RIF. TRIAL REGISTRATION: The University Hospital Medical Information Network (UMIN) Clinical Trial Registry: UMIN000036050 (date of registration: March 1, 2019).

New trial of progestin-primed ovarian stimulation using dydrogesterone versus a typical GnRH antagonist regimen in assisted reproductive technology.

PURPOSE: To compare the clinical and ongoing pregnancy rates between a protocol using oral dydrogesterone with human menopausal gonadotropin (HMG) for progestin-primed ovarian stimulation (PPOS) and the typical gonadotropin-releasing hormone (GnRH) antagonist regimen in women undergoing controlled ovarian hyperstimulation (COH). METHODS: This was a prospective, controlled study of 251 women who underwent COH for in vitro fertilization between October 2016 and July 2017. The patients were allocated alternately into two groups: a dydrogesterone protocol (study group) and a GnRH antagonist protocol (control group). In study group, dydrogesterone (20 mg/day) plus HMG (150 or 225 IU) were administered simultaneously beginning on days 2 or 3 of the menstrual cycle. In both groups, all high-quality embryos were cryopreserved for later transfer. The primary outcome was the ongoing pregnancy rate at 12 weeks per frozen-thawed embryo transfer (FET) and the secondary outcome was the clinical pregnancy rate. RESULTS: None of the patients experienced a premature luteinizing hormone surge. During the follow-up period, 397 FET cycles were completed. The ongoing pregnancy rates at 12 weeks were 40.0% in study group versus 38.1% in control group (absolute difference 1.9%; 95% CI - 6.83 to 17.2%). The clinical pregnancy rate in study group (52.8%) was also not inferior to that in control group (49.5%; absolute difference 3.3%; 95% CI - 4.02 to 20.2%). CONCLUSIONS: The clinical and ongoing pregnancy rates in study group were comparable to those in control group. Therefore, PPOS with dydrogesterone is a reasonable option to provide COH.

First case of vaginal radical trachelectomy in a pregnant Japanese woman.

A diagnosis of cervical cancer during pregnancy poses difficult management and ethical problems. Survival of the patient is the foremost concern, but fetal viability and well-being must also be addressed. Radical trachelectomy (RT) has recently begun to be performed as a possible treatment modality for early stage invasive uterine cervical cancer in pregnant patients who would like to continue their pregnancy. A 32-year-old Japanese woman visited a local hospital for prenatal care, and was diagnosed with a FIGO I B1 adenocarcinoma of the uterine cervix. She had a strong desire to avoid pregnancy termination, so she was admitted to our hospital for fertility-preserving surgery. After extensive counseling, vaginal radical trachelectomy with abdominal pelvic lymphadenectomy was performed in the 16th gestational week. The excised uterine cervix and lymph nodes were pathologically negative for cancer. To maintain her pregnancy, daily vaginal disinfection with povidone iodine, bed rest, and administration of ritodrine and an ulinastatin vaginal suppository were continued until the delivery. At 34 weeks' gestation, an emergency cesarean section was performed because of sudden premature rupture of the membranes. A baby girl was born weighing 2112 g, with Apgar score of 8/9. The mother remains without evidence of recurrence at the time of this report. This is the first case of successful pregnancy and delivery in Japan after vaginal RT.

New treatment strategy for endometriosis using progestin-primed ovarian stimulation with dienogest: A prospective cohort study, comparison of dienogest versus dydrogesterone.

Dienogest (DNG) is an oral progestin effective for the treatment of symptomatic endometriosis, such as reduction of endometrial lesion and control of pain intensity. Progestin-primed ovarian stimulation (PPOS) is a new controlled ovarian hyperstimulation (COH) regimen, and several reports have shown that dydrogesterone (DYG) is an appropriate progestin for PPOS. The purpose of this study was to evaluate the efficacy of DNG in patients undergoing PPOS during COH in comparison with DYG. This was a prospective, cohort, parallel-group, non-inferiority trial of 150 women with endometriosis undergoing assisted reproductive technology between February 2018 and May 2020 at the single fertility center. The assignment to each protocol was based on the optimal treatment for each patient. Patients taking DNG 2 mg continuously were assigned in the DNG group(n = 73). The other patients were allocated in DYG group(n = 77). All viable embryos were cryopreserved for subsequent transfer. The main outcome measures were the mature oocyte and fertilization rates. During this study, no premature LH surge was detected. A smaller number of oocytes were retrieved in the DNG group than in the DYG group (6.18 ± 3.60 vs. 9.85 ± 5.77); however, the rate of mature oocytes was significantly higher in the DNG group than in the DYG group (89.1 % vs. 78.9 %). The fertilization rate was comparable between two groups. Therefore, patients taking DNG for PPOS can continue endometriosis treatment and obtain good-quality embryos during COH. Further prospective randomized-controlled trial should be performed to confirm of this novel strategy of DNG.

Changes of uterine blood flow after vaginal radical trachelectomy (VRT) in patients with early-stage uterine invasive cervical cancer.

BACKGROUND: Vaginal radical trachectomy (RT) ligates and cuts several arteries supplying the uterus. Changes of blood supply to the uterus in two patients who experienced pregnancy and delivery were studied by using 3-D CT scanning. Effects of changes of blood supply to the uterus on the pregnancy courses were also examined. METHODS: Vascular distribution in the uterus was studied in two patients who received vaginal RT after delivery. Effects of changes of vascular distribution after vaginal RT were studied with respect to pregnancy courses and cervical functions. RESULTS: New arterial vascularization from the ascending branches of uterine arteries or other arteries occurred, and these new vessels seemed to supply blood to the remaining cervix. Differences of fetal growth and histopathological changes in the placenta between the two patients could not be detected. CONCLUSION: Ligation and cutting of several supplying arteries by RT induces new arterial vascularization and it does not seem to affect fetal growth and placental function.