Inappropriate gestational weight gain impact on maternofetal outcomes in gestational diabetes.

OBJECTIVE: To evaluate the association between the dimension of deviation from appropriate gestational weight gain (GWG) and adverse maternofetal outcomes in women with gestational diabetes mellitus (GDM). METHODS: We performed a multicentric retrospective study based on the Portuguese GDM Database. Women were classified as within GWG, insufficient (IGWG) or excessive (EGWG) than the Institute of Medicine recommendations. EGWG and IGWG were calculated for each prepregnancy BMI category. Large-for-gestational-age (LGA) and macrosomia were defined as a birthweight more than the 90th percentile for the gestational age and newborn weight greater than 4000 g, respectively. Logistic regression models (adjusted odds ratio [aOR] plus 95% confidence interval [95%CI]) were derived to evaluate the association between EGWG or IGWG and adverse maternofetal outcomes. RESULTS: A total of 18961 pregnant women were included: 39.7% with IGWG and 27.8% with EGWG. An EGWG over 3 kg was associated with a higher risk of LGA infants (aOR 1.95, 95%CI 1.17-3.26) and macrosomia (aOR 2.01, 95%CI 1.23-3.27) in prepregnancy normal weight women. An EGWG greater than 4 kg was associated with a higher risk of LGA infants (aOR 1.67, 95%CI 1.23-2.23) and macrosomia (aOR 1.90, 95%CI 1.38-2.61) in obese women. In overweight women, an EGWG above 3.5 kg was associated with a higher risk of LGA infants (aOR 1.65, 95%CI 1.16-2.34), macrosomia (aOR 1.85, 95%CI 1.30-2.64), preeclampsia (aOR 2.40, 95%CI 1.45-3.98) and pregnancy-induced hypertension (aOR 2.21, 95%CI 1.52-3.21). An IGWG below -3.1 kg or -3kg was associated with a higher risk of small-for-gestational-age [SGA] infants in women with normal (OR 1.40, 95%CI 1.03-1.90) and underweight (OR 2.29, 95%CI 1.09-4.80), respectively. CONCLUSIONS: Inappropriate gestational weight gain seems to be associated with an increased risk for adverse maternofetal outcomes, regardless of prepregnancy BMI. Beyond glycemic control, weight management in women with GDM must be a focus of special attention to prevent adverse pregnancy outcomes.KEY MESSAGESThe dimension of deviation from appropriate gestational weight gain was associated with an increased risk for adverse maternofetal outcomes among women with gestational diabetes.Weight management must be a focus of special attention in women with gestational diabetes to prevent adverse pregnancy outcomes.

C-type natriuretic peptide signaling in human follicular environment and its relation with oocyte maturation.

Studies in mice have shown that C-type natriuretic peptide (CNP) is produced by granulosa cells and contributes to ovarian follicle growth and oocyte meiotic arrest until the preovulatory LH surge. In humans, the relationship between intraovarian CNP levels and oocyte meiotic resumption is unknown. The aim of this study was to investigate whether CNP and its receptor NPR2 are expressed in human ovarian follicles and if their levels change according to the meiotic phase of oocytes. We collected follicular fluid (FF) and luteinized granulosa cells (LGC) from follicle pools (n = 47), and FF, LGC and cumulus cells (CC) from individual follicles (n = 96) during oocyte pickup for in vitro fertilization. There was a positive linear correlation between CNP levels in FF pools and basal antral follicle counting (rs = 0.458; p = 0.002), number of preovulatory follicles >16 mm (rs = 0.361; p = 0.016) and number of oocytes retrieved (rs = 0,378; p = 0.011) and a negative correlation between CNP levels in FF pools and the percentage of mature (MII) oocytes retrieved (rs = -0.39; p = 0.033). FF CNP levels in follicles containing MII oocytes were significantly lower than in follicles containing immature (MI) oocytes (median = 0.44 vs. 0.57 ng/mL, p < 0.05). Accordingly, the CNP precursor gene NPPC was 50% less expressed in LGC from follicles containing MII oocytes than in follicles containing MI oocytes (p < 0.01). In addition, NPR2 mRNA was down-regulated in CC surrounding MII oocytes (60% reduction, p < 0.01). CNP signaling is downregulated in human ovarian follicles containing mature oocytes. Further studies should clarify whether CNP signaling is essential to keep oocyte meiotic arrest in humans.

Caspase-3 gene expression in human luteinized granulosa cells is inversely correlated with the number of oocytes retrieved after controlled ovarian stimulation.

Granulosa cells control oocyte maturation through paracrine signalling and changes to the microenvironment around the oocyte. Apoptosis occurs as a physiological mechanism of granulosa cell renewal, but how it relates with the ovarian response to induced ovulation is still unclear. Therefore, this study evaluated apoptosis-related gene expression levels in granulosa cells of patients undergoing controlled ovarian stimulation. We enrolled prospectively 59 consecutive IVF patients referred to a tertiary academic hospital for couple infertility treatment. Luteinized granulosa cells were isolated from follicular fluid and the RNA was extracted, reverse-transcribed and the gene expression of apoptosis inducers (caspase-3, caspase-8 and bax) and inhibitor (Bcl-2) was quantified by real-time polymerase chain reaction. Caspase-3 gene expression correlated negatively with the number of pre-ovulatory follicles (Spearman's r = -0.308), the number of collected oocytes (r = -0.451), the number of mature oocytes (r = -0.526), the number of fertilized oocytes (r = -0.439) and the number of viable embryos (r = -0.443, all statistically significant at p < 0.02 level). No such associations were found with caspase-8, bax or bcl-2. These preliminary findings suggest that increased caspase-3 gene expression in granulosa cells is associated with a worse ovulatory response in humans.