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.

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.

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.

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.

Endometriosis and pregnancy outcome: are pregnancies complicated by endometriosis a high-risk group?

OBJECTIVES: Increased incidence of preterm birth, pregnancy-induced hypertension (PIH) and small-for-gestational-age (SGA) babies have been reported in women with endometriosis, but the study populations included women in whom a definitive diagnosis was not attainable, and women who conceived via in vitro fertilization/embryo transfer (IVF/ET), which, in itself, is a risk factor for adverse pregnancy outcome. Thus there is a lack of consensus on the effects of endometriosis on pregnancy outcome. This study compared the pregnancy outcomes of women with or without a definitive diagnosis of endometriosis on laparoscopy. STUDY DESIGN: Retrospective comparison of pregnancy outcomes of 108 women who underwent managed delivery of pregnancies established after laparoscopic investigation of infertility. Women with factors known to affect pregnancy outcome, such as age ≥41 years, conception via IVF/ET and multiple births, were excluded. Forty-nine of the study participants had endometriosis (En+ group) and 59 participants did not have endometriosis (En- group). RESULTS: There were no significant differences in mean (±standard deviation) age (33±3.8 vs 33.6±4.1 years), history of miscarriage, history of preterm birth and history of PIH between the two groups. Ovulation induction was used for infertility treatment in 26.5% of the En+ group and 30.5% of the En- group, and artificial insemination was used in 30.6% of the En+ group and 32.2% of the En- group. Regarding pregnancy outcomes, no significant differences in miscarriage (18.4% vs 18.6%), subchorionic haematoma (5.0% vs 2.1%), preterm birth (7.5% vs 8.3%), PIH (15.0% vs 12.5%), caesarean section (32.5% vs 22.9%), gestational age at delivery (38.9±1.5 vs 38.8±1.7 weeks), birth weight (3013.3±480 vs 2934.5±639.5g) and SGA babies (2.5% vs 2.1%) were found between the En+ and En- groups. Placental abruption did not occur in either group. One neonate had trisomy 21 in the En+ group, and one woman had gestational diabetes in the En- group. CONCLUSION: Endometriosis may not affect pregnancy outcome, but there is a need for a large prospective study.

Subchorionic hematoma occurs more frequently in in vitro fertilization pregnancy.

OBJECTIVE: Obstetric complications occur more frequently in pregnancies after in vitro fertilization (IVF). We attempted to determine the correlation between subchorionic hematoma and IVF pregnancies. STUDY DESIGN: We analyzed 194 pregnancies achieved by infertility treatment between January 2008 and February 2012 at our hospital. Among these, 67 were achieved by IVF and 127 by non-IVF approaches. We compared the frequency of subchorionic hematoma between the groups and examined the risk factors for subchorionic hematoma in the IVF group. RESULTS: No significant differences regarding age and the number of uterine surgery were observed between the groups. The duration of infertility was longer, parity and the rate of luteal support were higher in the IVF group compared with that in the non-IVF group. The frequency of subchorionic hematoma was significantly higher in the IVF group (22.4%) than that in the non-IVF group (11%) (P=0.035). Univariate analysis in the IVF group demonstrated that frozen-thawed embryo transfer (OR, 6.18; 95% CI, 1.7-22.4), parity≥1 (OR, 3.67; 95% CI, 1.0-13.2) and blastocyst transfer (OR, 3.75; 95% CI, 1.1-13.3) were risk factors for the subchorionic hematoma. CONCLUSION: The frequency of subchorionic hematoma is high in IVF pregnancies, and frozen-thawed embryo transfer, parity≥1, and blastocyst transfer may contribute to subchorionic hematoma onset.