Granulocyte colony-stimulating factor priming improves embryos and pregnancy rate in patients with poor ovarian reserve: a randomized controlled trial.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) administration increased ovarian preantral follicles and anti-Müllerian hormone (AMH) in animal models with diminished ovarian reserve. We investigated whether G-CSF priming before treatment with assisted reproductive technology (ART) improved embryo development and pregnancy rate while increasing serum AMH in patients with poor ovarian reserve. METHODS: In this prospective randomized open-label controlled trial, 100 patients 20 to 42 years old with AMH below 2 ng/mL were randomized to priming or control groups (50 patients each). None had over 1 ART failure, day-3 follicle-stimulating hormone (FSH) above 30 IU/L, uterine anomalies, or a partner with azoospermia. All patients initially underwent conventional infertility treatment for 2 consecutive cycles in which the priming group but not controls received a subcutaneous G-CSF priming injection during the early luteal phase. Each group then underwent 1 cycle of in vitro fertilization/intracytoplasmic sperm injection and fresh embryo transfer (IVF/ICSI-fresh ET), followed by cryopreserved ET if needed until live birth or embryo depletion. AMH was measured before and after priming. RESULTS: Fertilization rate, embryonic development, and implantation rate by fresh ET were significantly improved by priming. Clinical and ongoing pregnancy rates by IVF/ICSI-fresh ET were significantly higher with priming (30% and 26% in 47 ART patients; 3 delivered with conventional treatment) than in controls (12% and 10% in 49 ART patients; 1 dropped out). With priming, significantly more patients achieved cryopreservation of redundant blastocysts. The cumulative live birth rate was 32% in 50 patients with priming, significantly higher than 14% in 49 controls (relative risk, 2.8; 95% confidence interval, 1.04-7.7). Infants derived from priming had no congenital anomalies, while infant weights, birth weeks, and Apgar scores were similar between groups. Among 4 variables (age, day-3 FSH, AMH, and priming), logistic regression significantly associated age and priming with cumulative live birth. Priming significantly increased serum AMH. No adverse effects of priming were observed. CONCLUSION: G-CSF priming improved embryonic development and pregnancy rate during ART treatment and increased AMH in patients with poor ovarian reserve. Enhanced preantral follicle growth likely was responsible. TRIAL REGISTRATION: UMIN registration in Japan (UMIN000013956) on May 14, 2014.  https://www.umin.ac.jp/ctr/index.htm .

A case of recurrent hyperreactio luteinalis.

Hyperreactio luteinalis (HL) in normal pregnancy has been reported previously. However, only a few cases of HL recurrence have been reported. The present report describes HL in a normal singleton pregnancy presenting with an acute abdomen requiring surgical intervention. In a subsequent normal singleton pregnancy, HL recurred and was treated conservatively.

Treatment of endometrial hyperplasia with a danazol-releasing intrauterine device: a prospective study.

The purpose of the present study was to assess the effect of a danazol-releasing intrauterine device (D-IUD) in the treatment of endometrial hyperplasia. Twenty patients with endometrial hyperplasia including 14 with simple endometrial hyperplasia and 2 with complex endometrial hyperplasia (group A), and 4 with atypical endometrial hyperplasia (group B) were enrolled in the prospective study between August 1999 and December 2003. During and just after the treatment, improvement was seen in all patients. Simple or complex endometrial hyperplasia (group A) demonstrated regression to a normal secretory endometrium (38% of group A), pseudodecidual stromal change (31%) and glandular atrophy (25%), and miscellaneous change (inflammation, necrosis, etc.) (38%). Atypical hyperplasia (group B) demonstrated regression to a normal secretory endometrium (25% of group B), pseudodecidual stromal change (75%), glandular atrophy (50%) and miscellaneous change (granulation) (25%). In group A, 2 women conceived after completion of the treatment. The recurrence rate in patients with endometrial hyperplasia (groups A and B) in the follow- up was 20% and acceptable as compared with other studies. The pretreatment menstrual interval patterns of the patients were maintained peri- and post-treatment. These data indicate that D-IUD therapy might be a novel and effective method for the treatment of endometrial hyperplasia.