ObjectiveThe present study investigated long-term outcomes of medroxyprogesterone acetate (MPA) plus metformin therapy in terms of control of atypical endometrial hyperplasia (AEH) and endometrial cancer (EC), and post-treatment conception.MethodsWe retrospectively analyzed 63 patients (42 with EC; 21 with AEH) who underwent fertility-sparing management using MPA plus metformin. MPA (400 mg/day) and metformin (750–2,250 mg/day) were administered to achieve complete response (CR). Metformin was administered until conception, even after MPA discontinuation.ResultsOf the total patients, 48 (76%) had a body mass index (BMI) ≥25 kg/m2 and 43 (68%) showed insulin resistance. Sixty-one patients (97%) achieved CR within 18 months. CR rates at 6, 8–9, and 12 months were 60%, 84%, and 90%, respectively. During a median follow-up period of 57 months (range, 13–115 months), relapse occurred in 8 of 61 patients (13.1%) who had achieved CR. Relapse-free survival (RFS) in all patients at 5 years was 84.8%. Upon univariate analysis, patients with BMI ≥25 kg/m2 had significantly better prognoses than did those with BMI <25 kg/m2 (odds ratio=0.19; 95% confidence interval=0.05–0.66; p=0.009). Overall pregnancy and live birth rates per patient were 61% (19/31) and 45% (14/31), respectively.ConclusionsMPA plus metformin is efficacious in terms of RFS and post treatment conception. Moreover, metformin may be more efficacious for patients with BMI ≥25 kg/m2.

Background The World Health Organization does not recommend dilatation and sharp curettage (D&C) for the surgical treatment of miscarriage during the first trimester because this may cause Asherman’s syndrome due to endometrial damage; therefore, suction remains the primary treatment option. While manual vacuum aspiration (MVA) has been widely used since the 1990s outside Japan, the use of an MVA device (Women’s MVA system) was approved in Japan in October 2015. Here, we examined the efficacy of the MVA kit in women surgically treated for miscarriage. Methods This retrospective cohort study was conducted between 2014 and 2018 at the International University of Health and Welfare Hospital in Japan. Women who underwent surgical treatment for miscarriage within 12 weeks of pregnancy were identified and enrolled in the study. A total of 404 women were included who underwent the following procedures: 121 D&C, 123 electric vacuum aspiration (EVA), and 160 MVA. For each participant, the duration of surgery, amount of bleeding, amount of anesthetic used, incomplete abortion requiring repeat procedures, and intraoperative/postoperative complications were evaluated. Results The duration of surgery was 13.7 ± 7.2, 11.2 ± 4.2, and 6.9 ± 4.3 min in the D&C, EVA, and MVA groups, respectively (p = 1.00). The amount of anesthetic used was not significantly different among all groups. Bleeding of ≥ 100 mL was confirmed in three (2.4%), one (0.8%), and one (0.6%) patient(s) in the D&C, EVA, and MVA groups, respectively (p = 0.50). Incomplete abortion was identified in three (2.4%), two (1.6%), and one (0.6%) patient(s) in the D&C, EVA, and MVA groups, respectively (p = 0.61). However, severe intraoperative/postoperative complications were not observed in any group. Conclusions Surgical treatment for miscarriage performed using the MVA kit has safety and efficacy similar to those of conventional methods, such as D&C and EVA.

Brain damage caused by hypoxic ischemic insult during the perinatal period causes hypoxic ischemic encephalopathies (HIEs). Therapeutic hypothermia is indicated for HIE, but because the therapeutic burden is large for its limited therapeutic effectiveness, another strategy is needed. Progesterone (P4) plays a neuroprotective role through the actions of its metabolite, allopregnanolone (Allo), on P4 receptor, γ-aminobutyric acid type A receptors or both. We examined the therapeutic potential of P4 using a newborn rat model of HIE. Fetal rats were exposed to transient ischemic hypoxia by 30-minute bilateral uterine artery clamping on gestational day 18. After spontaneous birth, newborn pups were subcutaneously injected with P4 (0.10 or 0.01 mg), medroxyprogesterone acetate (MPA; 0.12 mg), or Allo (0.10 mg) through postnatal days (PDs) 1 to 9. Brain damage in the rats was assessed using the rotarod test at PD50. The HIE insult reduced the rats’ ability in the rotarod task, which was completely reversed by P4 and Allo, but not by MPA. Histological examination revealed that the HIE insult decreased neuronal (the cortex and the hippocampal CA1 region) and oligodendroglial cell density (the corpus callosum) through PD0 to PD50. The axon fiber density and myelin sheath thickness in the corpus callosum were also reduced at PD50. The time-course study revealed that P4 restored oligodendroglial cells by PD5, which was followed by neuroprotective action of P4 that lasted long over the injection period. These results suggest that P4 protects the neonatal brain from HIE insult via restoration of oligodendroglial cells.

Nonclassic congenital adrenal hyperplasia (NCAH) is an autosomal-recessive disorder caused by 21-hydroxylase deficiency and manifests as hirsutism and oligomenorrhea due to excess adrenal androgen and progesterone. We report a case of a woman with NCAH who showed continuous high serum progesterone levels in the follicular phase associated with impaired folliculogenesis. NCAH was diagnosed based on high 17-hydroxyprogesterone levels after rapid adrenocorticotropic hormone loading, and three heterozygous missense mutations in CYP21A2, encoding 21-hydroxylase, were identified. Recurrent failure of in vitro fertilization programs occurred because of empty follicles and preterm rupture of leading follicles, and vaginal stenosis with a hypoplastic cervix. Glucocorticoid administration normalized serum progesterone levels, restored folliculogenesis, and stretched the vaginal wall, which contributed to the success of the in vitro fertilization program. The patient delivered at term following blastocyst transfer. Correction of hyperandrogenism and high progesterone levels using glucocorticoids may improve fertility in women with NCAH.

Case series Patient:— Final Diagnosis: Acute fatty liver of pregnancy • HELLP syndrome Symptoms: Decrease in insulin dosage for gestational diabetes mellitus Medication: — Clinical Procedure:— Specialty: Obstetrics and Gynecology Objective: Unusual clinical course Background: When a woman becomes pregnant, the placenta produces human placental lactogen (hPL). The anti-insulin effect of hPL raises maternal blood glucose levels, allowing the fetus to use glucose as a nutrient. Because hPL is produced by the placenta until delivery, insulin requirements in patients with gestational diabetes mellitus (GDM) typically increase, but in some cases, they may decrease. We retrospectively examined data from women with GDM who received insulin and delivered at our hospital. Case Reports: From April 2019 to March 2020, we targeted patients who were diagnosed with GDM, received insulin, and delivered at our hospital. GDM was diagnosed based on the guidelines from the Japanese Society of Obstetrics and Gynecology. The rate of change in insulin dosage was calculated as: (insulin dosage at delivery – insulin dosage 14 days before delivery) divided by 14. Two patients whose insulin dosage was significantly reduced developed a syndrome of hemolysis, elevated liver enzymes, and low platelet count or acute fatty liver of pregnancy and underwent emergency cesarean section. Conclusions: The present case report suggests that a decrease in insulin requirement in pregnant patients with GDM can predict maternal abnormalities due to placental dysfunction.