Endometrial and vaginal microbiomes influence assisted reproductive technology outcomes.

OBJECTIVE: The role of Lactobacillus-dominant microbiota in the endometrium in reproductive function is unclear. We therefore aimed to explore the impact of the balance of Lactobacillus and pathological bacteria in the endometrial and vaginal microbiomes on the pregnancy outcomes of women treated with assisted reproductive technology (ART). METHODS: This study included 35 women with infertility submitted to good-quality embryo transfers. The cutoff values for abundance of Lactobacillus species (spp.) and pathological bacteria in the endometrium and vagina were calculated. Women with Lactobacillus spp. and pathological bacteria abundance above the cutoff values were categorized in the high-abundance group, whereas those with abundance below cutoff values were categorized in the low abundance group. We divided the patients into four groups based on the combination of high/low abundance of Lactobacillus spp. and pathological bacteria. RESULTS: The 35 cases of good-quality embryo transfer resulted in 21 pregnancies. Pregnant women were present in significantly higher proportions in the high Lactobacillus spp. abundance and low pathological bacteria abundance group, whereas the opposite combination (i.e., low Lactobacillus spp. abundance and high pathological bacteria abundance) saw a significantly higher proportion of nonpregnant women (p=0.022). CONCLUSIONS: The balance between Lactobacillus and pathological bacterial abundance in the endometrial and vaginal microbiomes is associated with pregnancy from ART.

Microbiome analysis in women with endometriosis: Does a microbiome exist in peritoneal fluid and ovarian cystic fluid?

Purpose: To investigate the relationship between the microbiome of the female genital tract and endometriosis. Methods: This prospective cohort study included 36 women who underwent laparoscopic surgery for ovarian tumor from July 2019 to April 2020. Of them, 18 had endometriosis, and 18 did not have endometriosis. Vaginal secretions, endometrial fluid, peritoneal fluid, and ovarian cystic fluid were collected during surgery. Next-generation sequencing of bacterial 16S rRNA was performed to characterize the microbiome. Results: Specific microbiomes were not detected in either peritoneal fluid or ovarian cystic fluid regardless of the presence or absence of endometriosis and the type of cyst. When the cutoff value of infectious bacterial abundance in the vagina was set as 64.3%, there were many cases more than a cutoff value in the endometriosis group significantly (p = 0.01). When the cutoff value of infectious bacterial abundance in the endometrium was set as 18.6%, there were many cases more than a cutoff level in the endometriosis cases significantly (p = 0.02). Conclusion: Peritoneal fluid and ovarian cystic fluid are almost sterile, although dysbiosis may occur in the vaginal and endometrial microbiome in women with endometriosis.

Two cases of polycystic ovary syndrome with onset of severe ovarian hyperstimulation syndrome following controlled ovarian stimulation with aromatase inhibitors for fertility preservation before breast cancer treatment.

OBJECTIVE: The risks of ovarian hyperstimulation syndrome (OHSS) involve high estrogen (E2) levels. We report two breast cancer patients with polycystic ovarian syndrome who underwent fertility preservation and had severe OHSS; their E2 levels were lowered using aromatase inhibitors (AI). CASE REPORTS: A 36-year-old woman underwent controlled ovarian stimulation (COS) with AI and cryopreserved 10 blastocysts. She was hospitalized with OHSS (E2 = 139.1 pg/mL). She improved with infusion alone. A 31-year-old woman underwent COS with AI and cryopreserved 8 blastocysts. She was hospitalized for OHSS (E2: 429 pg/mL). Her vascular endothelial growth factor (VEGF) levels were high (62 pg/mL) at 8 days after the procedure. She needed hospitalization for 9 days. The planned adjuvant therapy was delayed for a week in both cases. CONCLUSION: Elevated VEGF levels should be considered as a risk factor of OHSS even if E2 levels are low with AI treatment.

Live birth outcomes from IVF treatments in younger patients with low AMH.

OBJECTIVE: Anti-Müllerian hormone (AMH) is used to predict in vitro fertilization outcomes. However, predicting live birth is difficult in younger patients with low AMH. Thus, this study aimed to determine the live birth rates from younger patients with low anti-Müllerian hormone levels. METHODS: A total of 296 infertile patients with AMH measured (younger group, aged 25-38 years; older group, aged 39-42 years) were included in this study. In vitro fertilization outcomes between patients with AMH levels of <1.0ng/mL and ≥1.0ng/mL were compared. RESULTS: Younger patients with AMH levels <1.0ng/mL (younger low AMH group) exhibited lower number of oocytes retrieved than patients with AMH levels ≥1.0ng/mL (younger normal AMH group). However, there were no significant differences in cumulative pregnancy or cumulative live birth rates between groups. Older patients with AMH levels ≥1.0ng/mL (older normal AMH group) had significantly better outcomes as per mean number of oocytes, cumulative pregnancy rate, and cumulative live birth rate than older patients with AMH levels <1.0ng/mL (older low AMH group). In the younger low AMH group, the frequency of oocyte retrieval was significantly higher in patients who achieved live birth. In addition, the blastocyst transfer rate was significantly higher in individuals with live births versus subjects with non-live births. CONCLUSIONS: AMH is a predictor of live birth among older, but not younger, women. Our report suggests that younger women may become pregnant even with low AMH levels when they obtain blastocysts from frequent oocyte retrievals.

Sex ratio of infants born through in vitro fertilization and embryo transfer: Results of a single-institution study and literature review.

OBJECTIVE: The possible effects of Assisted Reproductive Technology (ART) on sex ratio at birth are extremely significant. This study aimed to determine whether ART affects the sex ratio of infants born through in vitro fertilization and embryo transfer (IVF-ET). MATERIALS AND METHODS: We ran this retrospective study on 290 singleton infants born following IVF-ET from February 2014 to August 2018 at a single institution. We compared the sex ratios of these infants with respect to insemination versus intracytoplasmic sperm injection (ICSI), early-cleavage embryo versus blastocyst transfer, fresh versus frozen-thawed embryo transfer and normal sperm versus asthenospermia. RESULTS: There were no significant differences in the sex ratio with respect to the fertilization method, transfer time, fresh embryo or frozen-thawed embryo transfer. In addition, the multiple logistic regression analysis revealed that these factors did not significantly affect the sex ratio. CONCLUSIONS: Our study indicated that the differences in the fertilization method transfer time and sperm motility rate did not affect the sex ratio of IVF live births. However, with increasing numbers of ICSI and blastocyst transfer cycles, factors possibly affecting the sex ratio need to be further investigated.

Impact of the one-carbon metabolism on oocyte maturation, fertilization, embryo quality, and subsequent pregnancy.

PURPOSE: To investigate impact of the one-carbon metabolism (OCM) on oocyte maturity and embryo development. METHODS: This prospective study analyzed 18 women who agreed to participate. We measured the OCM biomarkers' concentrations including Vitamin B12 (VB12), folic acid (FA), and homocysteine (Hcy) in serum and follicular fluid (FF), and assessed their correlation. We also evaluated the influence of such OCM biomarker concentrations in mono-FF on oocyte maturation, fertilization, embryo quality, and consequent pregnancy after embryo transfers. RESULTS: All biomarkers showed a high concentration variability in different follicles of each woman, but their mean levels correlated with the serum levels. Among the 106 collected oocytes, 92 were mature, 59 were fertilized, and 16 yielded good-quality embryos. We performed 26 single embryo transfers, and 7 patients achieved clinical pregnancies. VB12 concentration (FF) was significantly lower in fertilized than unfertilized oocytes by univariate analysis. In multivariate logistic analysis, a significant correlation was found between FA concentration (FF) <14.25 ng/mL and good-quality embryos and between Hcy concentration (FF) <4.9 nmol/mL and clinical pregnancy. CONCLUSION: OCM in FF may affect fertilization, embryo quality, and clinical pregnancy.

Silicone Plate for the Prevention of Postoperative Adhesions in Patients with Asherman Syndrome.

PURPOSE: Re-adhesion rates following hysteroscopic adhesiolysis have remained high. Accordingly, we present a case involving temporary placement of an intrauterine silicone plate to prevent re-adhesions following hysteroscopic adhesiolysis in a 36-year-old woman with Asherman syndrome. METHODS: After hysteroscopic adhesiolysis, a silicone plate molded to the uterine cavity's shape was inserted into the uterine cavity and left in place for 1 month. RESULTS: The patient had a history of endometrial curettage for endometrial polyps. After the procedure, she developed amenorrhea and experienced infertility for 5 years despite four cycles of in vitro fertilization and embryo transfer. Following admission to our hospital, hysteroscopic examination showed a wide area of intrauterine adhesions for which hysteroscopic adhesiolysis and silicone plate insertion were performed. The silicone plate was removed after 1 month. No intrauterine adhesions were observed during the subsequent hysteroscopic examination. After a thawed embryo transfer, the patient became pregnant and delivered a healthy baby. CONCLUSIONS: A silicon plate may be considered a useful tool for preventing re-adhesion following hysteroscopic adhesiolysis without serious complications.

Comparative study of obstetric and neonatal outcomes of live births between poor- and good-quality embryo transfers.

PURPOSE: To evaluate the effect of embryo quality on pregnancy outcomes. METHODS: This retrospective analysis included 80 live singleton births, resulting from morphologically good-quality embryo transfers, and 25 live singleton births that resulted from morphologically poor-quality embryo transfers between January, 2008 and December, 2014. Cleavage embryos that were graded as ≥2, according to the Veeck classification system, and blastocysts that were graded as ≥3BB, according to the Gardner classification system, were defined as good quality. The obstetric and neonatal outcomes were compared between the poor- and good-quality embryo transfer groups. RESULTS: The mean maternal age between the groups was similar. The blastocyst transfer rate was higher in the good-quality, than in the poor-quality, embryo transfer group. Other characteristics, including parity, infertility duration, the intracytoplasmic sperm injection rate, frozen-thawed embryo transfer rate, endometrial thickness, and hormone values before the embryo transfer, were similar between the groups. The obstetric and neonatal outcomes of live births between the two groups were not different in terms of preterm delivery, birthweight, small or large size for gestational age, malformation, umbilical artery cord pH of <7.20, hypertensive disorders of pregnancy, gestational diabetes mellitus, chorioamnionitis, placenta previa, and placental abruption. CONCLUSION: The obstetric and neonatal outcomes of live births between the poor- and good-quality embryo transfers were equivalent.

Spontaneous Regression of Uterine Arteriovenous Malformations with Conservative Management.

Uterine arteriovenous malformation (AVM) can cause massive hemorrhage and is often treated with uterine artery embolization (UAE), which may lead to ovarian insufficiency. Thus, avoiding UAE should be considered, particularly in women undergoing fertility treatments. We present three women diagnosed with postmiscarriage AVM on color Doppler by transvaginal ultrasound imaging. They had no genital bleeding and a small mass, measuring 16-22 mm. If estradiol was >300 pg/mL when AVM was diagnosed, then a gonadotropin-releasing hormone agonist was administered. All three women underwent follow-up observation, revealing spontaneous mass disappearance. To avoid ovarian insufficiency risk with UAE, conservative management and close follow-up observation should be considered in patients with AVM without bleeding, particularly during the fertility treatment.