Therapeutic effects of an oral gonadotropin-releasing hormone receptor antagonist, relugolix, on preventing premature ovulation in mild ovarian stimulation for IVF.

PURPOSE: Can relugolix, a novel oral gonadotropin-releasing hormone receptor (GnRH) antagonist, function as an alternative ovulation inhibitor to GnRH antagonist injections? METHODS: This single-center, cross-sectional retrospective study compared premature ovulation rates and clinical outcomes in IVF treatment after mild ovarian stimulation with 40 mg of relugolix (relugolix group) or 0.25-mg injections of ganirelix acetate or cetrorelix acetate (injection group) between March 2019 and January 2020. Of 247 infertile women (256 IVF cycles) aged ≤42 years, 223 women (230 cycles) were evaluated. In the relugolix and injection groups, we compared 104 and 85 cycles after GnRH antagonist use before the LH surge (LH levels <10 mIU/ml) and 22 and 19 cycles during the LH surge (LH levels ≥10 mIU/ml), respectively. RESULTS: Before the LH surge, the ovulation rates in the two groups were very low (p = 0.838), however; during the LH surge, the cycles using relugolix had a high ovulation rate of 40.9% compared with no ovulation in the injection group (p = 0.002). There were no significant differences in embryo culture findings and pregnancy outcomes between the two groups. CONCLUSIONS: Although relugolix had a high ovulation suppressive effect, when the LH surge occurred, its effect was insufficient.

Advanced scheduling for zygote intrafallopian transfer is possible via the use of a hormone replacement cycle for patients who have experienced repeated implantation failures.

PURPOSE: Zygote intrafallopian transfer (ZIFT) is an effective option for patients who have experienced repeated implantation failures (RIF) in assisted reproductive technology (ART) treatment. However, advance planning for the day of the operation can be problematic. Using a hormone replacement cycle (HRC) makes it possible to plan for the day of ZIFT. In the present study, we evaluated whether HRC-ZIFT is useful for RIF patients who have experienced difficulties obtaining morphologically good embryos in vitro. METHODS: A total of 55 patients with a history of five or more unsuccessful transfers received HRC-ZIFT between June 2008 and June 2013. The oocyte pick-ups were performed and the oocytes showing two pronuclei (2PN) were cryopreserved. After receiving more than five 2PN oocytes, the operation day was scheduled in advance, and as a consequence, a HRC was started and ZIFT was performed. The clinical outcomes were evaluated. RESULTS: The average age of the patients was 39.3 years, and the previous OPU and ET attempts numbered 7.5 and 6.9, respectively. The number of previously transferred embryos was 11.8, and the number of morphologically good embryos (MGEs) was only 1.2. The number of transferred 2PN oocytes was 6.7, and the subsequent pregnancy rate was 23.6 %. No ectopic or multiple pregnancies were observed, but there were 6 cases of miscarriage. CONCLUSION: Among RIF patients, in particular those who have difficulty obtaining MGEs in vitro, ZIFT might be a useful option. The HRC allows patients and medical staff to plan for the operation day in advance.

Using a mild stimulation protocol combined with clomiphene citrate and recombinant follicle-stimulating hormone to determine the optimal number of oocytes needed to achieve pregnancy and reduce the concerns of patients.

PURPOSE: The purpose of this study was to investigate how many oocytes are needed to achieve an adequate pregnancy rate per 1 oocyte retrieval cycle in mild ovarian stimulation. METHODS: This protocol consisted of clomiphene citrate and recombinant-follicle-stimulating hormone injection without a gonadotropin-releasing hormone-antagonist. From January 2009 through December 2010, there were 1,227 women who underwent assisted reproductive technologies treatment with mild stimulation at the Sugiyama Clinic. The overall pregnancy rate per single oocyte retrieval cycle was evaluated using both fresh and cryopreserved-and-thawed embryos according to the retrieved oocyte number. RESULTS: According to the retrieved oocyte number, a total of 1,227 cycles were divided into 4 groups: group A (the oocyte number <4; 433 cycles), group B (the oocyte number = 4, 5; 317 cycles), group C (the oocyte number = 6, 7; 206 cycles), and group D (the oocyte number ≥8; 271 cycles). The overall pregnancy rates for groups A, B, C, and D were 22.2, 42.9, 52.4, and 56.0 %, respectively, the rates for groups C and D were significantly higher than that for group A (p < 0.01). CONCLUSIONS: The optimal number of retrieved oocytes proved to be between 6 and 7 for the patients who received our milder stimulation protocol and experienced no reduction in their overall pregnancy rate.

Effects of Periconceptional Multivitamin Supplementation on Folate and Homocysteine Levels Depending on Genetic Variants of Methyltetrahydrofolate Reductase in Infertile Japanese Women.

Methylenetetrahydrofolate reductase (MTHFR) has various polymorphisms, and the effects of periconceptional folic acid supplementation for decreasing neural tube defects (NTDs) risk differ depending on the genotypes. This study analyzed the effectiveness of multivitamin supplementation on folate insufficiency and hyperhomocysteinemia, depending on MTHFR polymorphisms. Of 205 women, 72 (35.1%), 100 (48.8%) and 33 (16.1%) had MTHFR CC, CT and TT, respectively. Serum folate and homocysteine levels in women with homozygous mutant TT were significantly lower and higher, respectively, than those in women with CC and CT. In 54 women (26.3% of all women) with a risk of NTDs, multivitamin supplementation containing folic acid and vitamin D for one month increased folate level (5.8 ± 0.9 to 19.2 ± 4.0 ng/mL, p < 0.0001) and decreased the homocysteine level (8.2 ± 3.1 to 5.8 ± 0.8 nmol/mL, p < 0.0001) to minimize the risk of NTDs in all women, regardless of MTHFR genotype. Regardless of MTHFR genotype, multivitamin supplements could control folate and homocysteine levels. Tests for folate and homocysteine levels and optimal multivitamin supplementation in women with risk of NTDs one month or more before pregnancy should be recommended to women who are planning a pregnancy.

Impact of chronic endometritis on endometrial receptivity analysis results and pregnancy outcomes.

BACKGROUND: The aim of this study is to evaluate the relationship between chronic endometritis (CE) and a personalized window of implantation (WOI), identified by results of endometrial receptivity analysis (ERA), and pregnancy outcomes following embryo transfer (ET) based on the ERA outcomes. METHODS: The single-center, cross-sectional study was designed. The study population consisted of 101 infertile women who underwent endometrial sampling between June 2018 and February 2020. We recruited 88 patients who underwent ERA testing and immunohistochemistry of the plasma cell marker CD138 to diagnose CE within 3 months of testing. Subjects were divided into three groups as follows: 33 without CE (non-CE group); 19 with untreated CE at ERA testing (CE group); and 36 successfully treated for CE before ERA testing (cured-CE group). CE diagnosis was defined as ≥5 CD138-positive plasma cells per 10 random stromal areas at ×400 magnification. RESULTS: In non-CE, CE, and cured-CE groups, the numbers of CD138-positive cells were 0.7 ± 1.0, 28.5 ± 30.4, and 1.3 ± 1.3, respectively (p < .001). The rates of "receptive" endometrium in non-CE and cured-CE groups were 57.6% (19 women) and 50.0% (18 women), respectively; however, in the CE group, this rate was significantly lower than the other two groups (p = .009) at only 15.8% (3 women). After CE were treated prior or posterior to the ERA test in cured-CE or CE groups, the clinical pregnancy rates at the first ET in non-CE, CE, and cured-CE groups were 77.8% (21/27 cycles), 22.2% (4/18 cycles), and 51.7% (15/29 cycles), respectively (p < 0.001). CONCLUSION: CE had detrimental effects on the individual WOI, leading to embryo-endometrial asynchrony; therefore, diagnosis and treatment of CE should be done before ERA testing.

Influence of red blood cell concentration on the initiation time of blood coagulation: risk of thrombus formation in pregnant females with anemia.

The influence of a change in red blood cell (RBC) concentration on the initiation time of blood coagulation (Ti) in pregnant and non-pregnant females was investigated using a damped oscillation rheometer to evaluate the risk of hemorrhagic tendency or thrombus formation. The blood samples from 40 female volunteers (20 pregnants and 20 non-pregnants) were examined. After centrifuging some portion of each blood sample, an appropriate volume was taken from the RBC layer to make an artificially diluted blood, or to add it to the autologous blood, making an artificially concentrated blood. The Ti of non-pregnant females was significantly reduced with increasing the RBC concentration from 3.75+/-0.25 to (5.75+/-0.25)x10(6)/mm(3). However, the Ti of pregnant females showed almost no change in the RBC concentrations from 3.25+/-0.25 to (5.25+/-0.25)x10(6)/mm(3). These results suggest that RBC concentration plays an important role in accelerating the initial coagulation reaction of blood of non-pregnant females and that a hypercoagulant condition caused by pregnancy conceals the effect that changes in RBC concentration have in pregnant females.