Serum PAPP-A levels at 10-14 weeks of gestation are altered in women after assisted conception

OBJECTIVES: Increased screen-positive rate was observed in the first-trimester screening for trisomy 21 (T21) among women after assisted conception. The aim of this study was to identify the trends of changes in serum marker levels after different modes of assisted conception. METHODS: Retrospectively, we analyzed the levels of free beta human chorionic gonadotrophin (f beta HCG), pregnancy-associated plasma protein-A (PAPP-A) and inhibin A in maternal serum, and fetal nuchal translucency (NT) thickness at 10-14 gestational weeks in 1098 women with singleton pregnancies: 130 after IVF-ET, 54 after ICSI and 914 after spontaneous conception. RESULTS: In women after IVF-ET and ICSI, PAPP-A was decreased (0.94 MoM and 0.82 MoM, respectively) and inhibin A increased (1.11 MoM and 1.48 MoM, respectively) in comparison to the women after spontaneous conception. With increasing number of oocytes retrieved PAPP-A decreased and inhibin A increased. In women pregnant after assisted conception without ovarian stimulation (transfer of frozen-thawed embryo or in spontaneous cycle) the marker levels were not significantly different from those in women after spontaneous conception. CONCLUSIONS: The presence of multiple corpora lutea may be responsible for the changes in marker levels. In spite of the differences in marker levels, the screen-positive rate for T21 is not significantly increased in women after assisted conception.     

Elevated maternal midtrimester serum free beta-human chorionic gonadotropin levels in vegetarian pregnancies that cause increased false-positive Down syndrome screening results

OBJECTIVE: The aim of this study was to examine whether midtrimester maternal serum free beta-human chorionic gonadotropin and alpha-fetoprotein levels for Down syndrome screening differed in vegetarian pregnancies and omnivore pregnancies and to evaluate whether maternal serum vitamin B(12) concentration affected these maker levels. STUDY DESIGN: Ninety-eight vegetarian and 122 omnivore singleton pregnancies were studied. Reference levels of free beta-human chorionic gonadotropin and alpha-fetoprotein were based on a population of 6312 singleton euploid pregnancies that had been surveyed previously. Serum free beta-human chorionic gonadotropin and alpha-fetoprotein levels were measured by enzyme immunoassay or radioimmunoassay. Multiples of the median values were calculated to determine whether different diet habits affected serum biomarker levels. Maternal serum vitamin B(12) levels were determined with radioimmunoassay. RESULTS: The free beta-human chorionic gonadotropin multiples of the median values were elevated significantly in the vegetarian pregnancies group (1.28 multiples of the median) compared with that of the reference population (1.00 multiples of the median) (P<.001). A negative association between the serum free beta-human chorionic gonadotropin multiples of the median values and the concentration of maternal serum vitamin B(12) was observed in the vegetarian pregnancies. No correlation was found between the alpha-fetoprotein multiples of the median values and the maternal serum vitamin B(12) concentration. CONCLUSION: The current data showed that the midtrimester maternal serum free beta-human chorionic gonadotropin levels increased in vegetarian pregnancies and led to an elevated false-positive rate in screening for Down syndrome compared with pregnant women with regular diet and resulted in unnecessary invasive procedures. It is necessary to establish vegetarian pregnancy alpha-fetoprotein and beta-human chorionic gonadotropin reference levels to correct increased false-positive screening results.     

Initial maternal serum human chorionic gonadotropin levels in pregnancies achieved after assisted reproductive technology are higher after preimplantation genetic screening and after frozen embryo transfer: a retrospective cohort

Purpose

Few published articles have compared initial hCG values across all different types of ART cycles, including cycles with fresh or frozen embryo transfer. No articles have compared initial hCG values in cycles utilizing preimplantation genetic screening (PGS). The purpose of this study is to compare initial hCG values after fresh embryo transfer, frozen embryo transfer, and after PGS.

Methods

This was a single-center retrospective cohort study at an academically affiliated private IVF center. All fresh and frozen embryo transfers between January 2013 and December 31, 2015 were included. We compared mean initial serum hCG values 14 days after oocyte retrieval for fresh cycles and 9 days after frozen embryo transfer. We examined cycles of single embryo transfer (SET) and double embryo transfer (DET).

Results

Two hundred elven IVF (fresh embryo transfer), 128 FET (frozen embryo transfer cycles, no PGS), and 111 PGS cycles (ovarian stimulation with embryo cryopreservation, PGS, and frozen transfer in a subsequent estrogen-primed cycle) with initial positive hCG values were analyzed. In patients achieving a positive hCG after SET, initial hCG values were higher after PGS compared to FET (182.4 versus 124.0 mIU/mL, p = 0.02) and IVF (182.4 versus 87.1 mIU/mL, p < 0.001) as well as FET compared to IVF (124.0 versus 87.1 mIU/mL, p < 0.01). After DET, initial hCG values were higher after PGS (222.8 mIU/mL) compared to FET (182.1 mIU/mL, p = 0.02) and IVF (131.1 mIU/mL, p = 0.001).

Conclusions

Our study suggests that initial serum hCG values are higher after using PGS and higher after the transfer of a frozen embryo compared to a fresh embryo. This suggests that initial hCG values relate to the chromosomal status of embryos. Initial hCG values may help determine intervention and monitoring later in pregnancy.

     

Highly abnormal maternal inhibin and beta-human chorionic gonadotropin levels along with severe HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome at 17 weeks' gestation with triploidy

A 17-week pregnancy complicated by severe hypertension is reported. The fetus had multiple anomalies and was found to have triploidy. Assay of maternal serum markers for trisomy 21 revealed elevated levels of inhibin (137.51 multiples of the median) and human chorionic gonadotropin (41.51 multiples of the median).     

Prolonged gonadotropin stimulation for assisted reproductive technology cycles is associated with decreased pregnancy rates for all women except for women with polycystic ovary syndrome

Purpose

To determine if etiology of infertility modifies the relationship between the duration of ovarian stimulation and success during assisted reproductive technology (ART) cycles.

Methods

A prospectively collected database was analyzed in an academic infertility practice. Eight hundred and twelve infertile women undergoing their initial fresh embryo, non-donor in vitro fertilization (IVF) or Intracytoplasmic Sperm Injection ICSI) cycle between January 1999 and December 2010 were evaluated. Clinical pregnancy was the main outcome measured.

Results

Out of 663 cycles resulting in oocyte retrieval, 299 produced a clinical pregnancy (45.1%). Women who achieved a clinical pregnancy had a significantly shorter stimulation length (11.9 vs. 12.1 days, p=0.047). Polycystic ovary syndrome (PCOS) was the only etiology of infertility that was significantly associated with a higher chance for clinical pregnancy and was a significant confounder for the association of duration and success of treatment. Women with 13 days or longer of stimulation had a 34 % lower chance of clinical pregnancy as compared to those who had a shorter cycle (OR 0.66, 95% CI:0.46-0.95) after adjustment for age, ovarian reserve, number of oocytes retrieved, embryos transferred and PCOS diagnosis.

Conclusion

Prolonged duration of stimulation is associated with decreased ART success for all couples, except for women with PCOS.     

The influence of fetal sex in screening for trisomy 21 by fetal nuchal translucency, maternal serum free beta-hCG and PAPP-A at 10-14 weeks of gestation

In a study of 2923 normal pregnancies and 203 pregnancies affected by trisomy 21 we have shown a significant difference in the median MoM of the markers: fetal nuchal translucency, maternal serum free beta-hCG and PAPP-A in the presence of a female fetus compared with a male fetus. For maternal serum free beta-hCG levels are higher by 15% if the fetus is chromosomally normal and by 11% if the fetus has trisomy 21. For maternal serum PAPP-A the levels in chromosomally normal fetuses are 10% higher in the presence of a female fetus and 13% higher if the fetus has trisomy 21. In contrast, fetal nuchal translucency is 3-4% lower in both chromosomally normal and trisomy 21 female fetuses. The consequence of such changes when screening for trisomy 21 will be a reduction in the detection rate in female fetuses by a factor of 1-2%. Correction of risk algorithms for fetal sex, however, is probably not feasible, since ultrasound detection of fetal sex is only 70-90% accurate in the 10-14 week period.