Levels of angiogenic markers in second-trimester maternal serum from in vitro fertilization pregnancies with oocyte donation.

OBJECTIVE: To determine whether differences exist in angiogenic placental growth factor (PlGF) and antiangiogenic soluble vascular endothelial growth factor receptor 1 (sVEGFR-1; both being early markers of placental ischemic disease) in oocyte-donation (OD) pregnancies, compared with autologous in vitro fertilization (aIVF) and spontaneous pregnancies. DESIGN: Case-control study of residual second-trimester serum samples from women undergoing prenatal screening. SETTING: Academic medical center. PATIENT(S): Fifty-seven OD pregnancies were identified. Each OD pregnancy was matched to two spontaneous pregnancies (n = 114) and one aIVF pregnancy (n = 57). INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): Second-trimester serum PlGF and sVEGFR-1 levels. RESULT(S): sVEGFR-1, PlGF, and unconjugated E2 levels were similar among the three study groups. The ratio of sVEGFR-1 to PlGF was significantly higher in the OD group. Consistently with previous studies, alpha-fetoprotein (AFP) in the OD group was significantly elevated compared with spontaneous pregnancy. Both aIVF and OD groups had greater levels of inhibin A than the spontaneous pregnancy group, and the OD group had significantly higher levels of inhibin A than the aIVF group. hCG levels were significantly elevated in aIVF compared with spontaneous pregnancy; however, levels were not different between aIVF and OD. CONCLUSION(S): Second-trimester serum sVEGFR-1 and PlGF levels were not significantly altered in OD pregnancies. Our data support previous findings that OD pregnancies have uniquely increased second-trimester AFP, hCG, and inhibin A levels compared with aIVF. However, the biologic basis of these marker elevations in OD may not be related to placental angiogenesis.

Minichromosome maintenance complex component 8 and 9 gene expression in the menstrual cycle and unexplained primary ovarian insufficiency.

PURPOSE: DNA repair genes Minichromosome maintenance complex component (MCM) 8 and 9 have been linked with gonadal development, primary ovarian insufficiency (POI), and age at menopause. Our objective was to characterize MCM 8 and 9 gene expression in the menstrual cycle, and to compare MCM 8/9 expression in POI vs normo-ovulatory women. METHODS: Normo-ovulatory controls (n = 11) and unexplained POI subjects (n = 6) were recruited. Controls provided three blood samples within one menstrual cycle: (1) early follicular phase, (2) ovulation, and (3) mid-luteal phase. Six of 11 controls only provided a follicular phase sample. Amenorrheic POI subjects provided a single, random blood sample. MCM8/9 expression in peripheral blood was assessed with qRTPCR. Analyses were performed using delta-Ct measurements; group differences were transformed to a fold change (FC) and confidence interval (CI). Differences across menstrual cycle phases were compared using random effects ANOVA. Two-sample t tests were used to compare two groups. RESULTS: MCM8 expression was significantly lower at ovulation and during the luteal phase, when compared to the follicular phase [FC = 0.69 in the luteal vs follicular phase (p = 0.012, CI = 0.53, 0.90); and 0.65 in the ovulatory vs follicular phase (p = 0.0057, CI = 0.50, 0.85)]. No change in MCM9 expression was noted throughout the menstrual cycle. No significant difference was seen in MCM8/9 expression when comparing POI to control subjects. CONCLUSIONS: Our study showed greater MCM8 expression in the follicular phase of the menstrual cycle, compared to the ovulatory and luteal phases. No cyclic changes were seen with MCM9. Significant differences in MCM8/9 expression were not detected between POI and controls; however, we recommend further investigation with a larger sample population.

The Value of Anti-Müllerian Hormone in Predicting Clinical Pregnancy After Intrauterine Insemination.

OBJECTIVES: To evaluate the utility of anti-Müllerian hormone (AMH) in predicting clinical pregnancy with intrauterine insemination (IUI) and compare it to other markers of quantitative ovarian reserve. METHODS: Retrospective cohort study of women undergoing natural and stimulated IUI cycles. All patients achieved a clinical pregnancy within three IUI cycles or completed three IUI cycles without pregnancy. Receiver operating curves were generated to determine the ability of AMH, antral follicle count, age, BMI, and day 3 FSH to predict clinical pregnancy with IUI. Characteristics of those with and without pregnancy were compared using Mann-Whitney U, chi-square, and Fisher exact tests. RESULTS: Of 209 women included, 49% achieved clinical pregnancy. Pregnant patients were more likely to have a higher AMH (2.76 vs. 1.55 ng/mL, P = 0.0004). The area under the curve was 0.642 in predicting clinical pregnancy within three IUI cycles using AMH (0.608 if excluding polycystic ovarian syndrome patients); 0.639 using antral follicle count; 0.549 using age; 0.599 using day 3 FSH; and 0.639 using BMI. CONCLUSION: Although serum AMH appears significantly higher in women achieving clinical pregnancy, the predictive value of AMH alone was no better than that for other markers of quantitative ovarian reserve in a patient who clinically qualifies for IUI.

Blastocyst transfer is not associated with increased rates of monozygotic twins when controlling for embryo cohort quality.

OBJECTIVE: To compare monozygotic twinning (MZT) rates in patients undergoing blastocyst or cleavage-stage ET. DESIGN: Retrospective cohort. SETTING: Academic research center. PATIENT(S): Autologous, fresh IVF cycles resulting in a clinical pregnancy from 1999 to 2014. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Monozygotic twin pregnancy in blastocyst-stage transfer vs. cleavage-stage transfer when controlling for patient prognosis and embryo cohort quality factors. RESULT(S): There were a total of 9,969 fresh transfer cycles resulting in a pregnancy during the study period. Of these pregnancies, 234 monozygotic twin pregnancies were identified (2.4%). Of all transfers, 5,191 were cleavage-stage and 4,778 were blastocyst-stage transfers. There were a total of 99 MZT identified in the cleavage-stage group (1.9%) and 135 MZT in the blastocyst ET group (2.4%), which was significant. Multivariable logistic regression revealed that increasing age was associated with a significant reduction in MZT, regardless of transfer order. Embryo cohort quality factors, including the number and proportion of six- to eight-cell embryos and availability of supernumerary embryos, were also significant. When controlling for patient age, time period during which the cycle took place, the number and proportion of six- to eight-cell embryos, and availability of supernumerary embryos, there was no longer a difference in MZT rate between blastocyst and cleavage transfer. CONCLUSION(S): Patient prognosis and embryo cohort quality seem to be major factors in MZT rate in women undergoing blastocyst transfer. Although technology-based effects cannot be excluded, patient and embryo characteristics play an important role.