Ben Schwartz is Associate Editor, Contemporary OB/GYN.
A recently published meta-analysis has found a relationship between a woman’s vitamin D levels and the success rate of assisted reproduction therapy (ART). Plus: Is progesterone effective in preventing preterm birth? Also: Results of a large cohort study show that women whose BMI is below or above normal before pregnancy may be at increased risk of complications or death associated with birth.
A recently published meta-analysis in Human Reproduction has found a relationship between a woman’s vitamin D levels and the success rate of assisted reproduction therapy (ART). The researchers found that women undergoing ART who have sufficient levels of vitamin D have a higher live birth rate than women who are vitamin D deficient.
Using a systematic review and meta-analysis of 11 published cohort studies, which included 2700 women, the researchers looked at primary articles that studied women undergoing any form of ART (In vitro fertilization [IVF], intracytoplasmic sperm injection [ICSI], and frozen embryo transfer [FET]) and also had their vitamin D status checked. The primary outcome was live birth rates according to vitamin D status and secondary outcomes included biochemical pregnancy rates and clinical pregnancy rates. Two of the researchers assessed the quality of the studies by using the Newcastle-Ottawa Quality Assessment Scales. The researchers extracted live birth, biochemical pregnancy, clinical pregnancy and miscarriage rates from each of the included studies according to Vitamin D levels.
Of the 11 studies, live birth was reported in seven of them, which included 2026 patients. Live birth was found to be more likely in women with sufficient levels of vitamin D when compared to with deficient levels of vitamin D (OR 1.33 [1.08-1.65]). Five studies (1700 patients) found that women replete in vitamin D were more likely to achieve a positive pregnancy test than women deficient in vitamin D (OR 1.34 [1.04-1.73]). All 11 of the studies, reported clinical pregnancy as an outcome. Clinical pregnancy was found to be more likely in women with replete levels of vitamin D (OR 1.46 [1.05-2.02]). Six studies (1635 patients) reported miscarriage by vitamin D concentrations, but no association between vitamin D levels and miscarriage were found (OR 1.12 [0.81-1.54]).
The researchers note a couple of limitations with their study. All of the included studies looked primarily at heterogeneous populations and fertility treatment protocols. But ultimately, the researchers note that their findings illustrate a connection between vitamin D levels and fertility likelihood. While vitamin D deficiency has been associated with abnormal pregnancy implications, the researchers suggest that vitamin D levels might also play a role in early pregnancy outcomes as well.
Is progesterone effective in preventing preterm birth?
A meta-analysis study published in the American Journal of Obstetrics and Gynecology provides additional validation for using progesterone to reduce the risk of preterm birth (PTB), neonatal complications and infant mortality in pregnant women with a short cervix. The researchers used individual patient data and found that vaginal progesterone reduces the rate of PTB in singleton pregnancies and would also be cost effective.
Looking at data from five randomized controlled trials that compared vaginal progesterone vs. placebo or no treatment, the researchers used individual patient data for 974 women with a cervical length £ 25 mm. Of those 974 women, 498 were assigned to vaginal progesterone and 476 to placebo. Two of the trials analyzed were specifically designed to evaluate use of vaginal progesterone in women with a short cervix (cervical length £ 15 mm and cervical length between 10 and 20 mm). One study tested the effect of vaginal progesterone in at-risk women for PTB because of previous spontaneous preterm pregnancies (SPTB). Another study evaluated use of vaginal progesterone in women at risk for PTB because of previous SPTB, a positive fibronectin test, or a sonographic cervical length £ 25 mm. The last study looked at use of vaginal progesterone in women with a history of SPTB, uterine malformations, or twin gestations. Three studies provided 96% of the total sample size of the individual patient data meta-analysis.
The researchers found that vaginal progesterone significantly reduced the risk of PTB birth < 33 weeks’ gestation (14% vs 22%; RR 0.62, 95% CI 0.47 – 0.81). The total frequencies of giving birth < 36, < 35, < 34, < 32, < 30, and < 28 weeks’ gestation and SPTB at < 33 and < 34 weeks were also significantly lower in the vaginal progesterone group (RRs from 0.64 to 0.80). Also in the vaginal progesterone group, the mean gestation age at delivery was significantly greater than in the placebo group (mean difference 0.74 weeks, 95% CI 0.18-1.30). The authors noted that vaginal progesterone treatment was associated with a significant decrease in risk of respiratory distress syndrome, composite neonatal morbidity, very low birthweight (< 1500 and < 2500 g) and admission to the neonatal intensive care unit. The frequency of neonatal mortality was 1.4% (7/498) in the vaginal progesterone group and 3.2% (15/476) in the placebo group.
The authors also reviewed cost-effectiveness studies on vaginal progesterone and found that measuring the uterine cervix with ultrasound in mid-trimester and giving vaginal progesterone to patients with a short cervix is a cost-effective strategy. One evaluated study estimated that it would save approximately $19.6 million for every 100,000 women screened.
Is pre-pregnancy BMI associated with maternal morbidity?
Results of a large cohort study show that women whose body mass index (BMI) is below or above normal before pregnancy may be at increased risk of complications or death associated with birth. The study, by investigators from Washington State, was published in JAMA.
The findings reflect analysis of outcomes in 743,630 pregnant women who had singleton births in Washington State from 2004 to 2013. Linked birth certificates and hospitalization files were used to collect demographic data and morbidity diagnoses.
The investigators looked at composite severe maternal morbidity or mortality including life-threatening conditions or conditions leading to serious sequelae, complications that required intensive care unit admission, and maternal death. With logistic regression, adjusted odds ratios (ORs) and adjusted rate differences were calculated with 95% confidence intervals (Cis) and adjustment for confounders such as maternal age and parity.
Of the women, 3.2% were underweight before pregnancy, 47.5% were normal weight, 25.8% were overweight, 13.1% were obesity class 1, 6.2% were obesity class 2, and 4.2% were obesity class 3. The rates of severe maternal morbidity or mortality per 10,000 women in those BMI categories were 171.5, 143.2, 160.4, 167.9, 178.3, and 202.9, respectively. Adjusted ORs were 1.2 for underweight women, 1.1 for overweight women and those with class 1 obesity, 1.2 for women with class 2 obesity, and 1.4 for women with class 3 obesity compared with those with normal BMI. Absolute risk increases were 28.8 for underweight women, 17.6 for overweight women, 24.9 for those with class 1 obesity, 35.8 for those with class 2 obesity, and 61.1 for women with class 3 obesity.
The authors concluded that in pregnant women in Washington State, low and high pre-pregnancy BMI were associated with a statistically significant but small absolute increase in severe maternal morbidity or mortality.