The trial, which took place in Singapore, New Zealand, and the UK, compared the effects of two types of supplements on the time required to conceive.
Over 1,700 women aged 18 to 38 from the three countries took part in the trial.
The intervention group took twice per day a powder sachet containing myo-inositol, probiotics Lactobacillus rhamnosus NCC4007 and Bifidobacterium animalis sp. Lactis NCC2818, and micronutrients vitamins B2, B6, B12, D, and zinc.
The control group, on the other hand, took a standard micronutrient supplement containing folic acid, iron, calcium, iodine, and beta-carotene.
Existing understanding shows that optimising micronutrient intake may directly improve ovarian function, as well as indirectly promote fertility by increasing glucose metabolism.
This in turn suppresses hyperinsulinemia and hyperandrogenism that impair ovarian functions.
For instance, vitamin B6 and B12 are found to be vital for the maturation of oocyte – a cell in the ovary, while vitamin D insufficiency is linked with insulin resistance and polycystic ovary syndrome (PCOS).
Writing in Fertility and Sterility, the researchers showed that the intervention was especially useful in women who were overweight. However, overall, the intervention group did not see a significantly shorter time-to-conception as compared to the control group.
“Compared with control, the intervention shortened time-to-conception among overweight women towards that of non-overweight/non-obese women,” the researchers said.
Findings showed that 20 per cent of the overweight women from the intervention group took 84.5 days to conceive.
Overweight women from the control group, however, took a longer time to conceive at 117 days.
Notably, the intervention has shortened the time-to-conception in the overweight women comparable to that of non-overweight women – who took 82.1 days to conceive.
“The chance of conceiving in the overweight intervention group was 1.47 times that of the overweight control group by the end of a year, becoming equivalent to that of non- overweight/non-obese women,” the researchers said.
They explained that this could be because the myo-inositol, probiotics, and micronutrient supplementation had improved the regulation of inflammatory factors, such as the c-reactive protein (CRP).
“Exploratory analyses suggest that a potential underlying mechanism for shortening time-to-conception could be suppression of inflammation by the intervention during the preconception period.
“This is supported by a lower CRP trend seen in the overweight intervention group as compared with the overweight controls.”
Cited the findings from Radin RG et al, the researchers added that lower CRP has been associated with better fertility, improved ovulatory function and endometrial receptivity, hence the chances of conception and successful implantation.
Worse results for obese women
However, the intervention had reportedly lengthened the time-to-conception among non-White women who were obese.
Obesity is defined as having a body mass index (BMI) greater than or equal to 30, while overweight is defined as having a BMI greater than or equal to 25.
“Among women with obesity, the intervention lengthened time-to-conception, an effect confined to non-white women with obesity, where the chance of conceiving in the intervention group was lowered to less than half that of the control group,” said the researchers.
They explained that the longer time-to-conception in older, obese, and metabolically less healthy women validated that the trial population behaved as expected. This means that the study subjects recruited were not unrepresentative of the overall population.
The existing understanding is that a higher maternal age, higher BMI, increased psychological stress, menstrual irregularity, no previous pregnancy, and higher HbA1c are all associated with a longer time-to-conception.
Country analysis
A country analysis showed that women in Singapore conceived slower than women in the UK or New Zealand, a novel finding of this study.
It took 151 days for 20 per cent of the women in Singapore to conceive, longer than 74 days in the UK and 80.5 days in New Zealand.
In Singapore, South Asian women and Chinese women were not significantly different in terms of time-to-conception at 185 days and 103.6 days respectively. Malay women, however, took a significantly longer time to conceive at 284.5 days.
In UK and New Zealand, white women conceived more quickly than non-white women, at 73 days versus 102.4 days.
“A novel finding is the variation in time-to-conception between ethnic groups, with a shorter time-to-conception in White compared with non-White women, and also in Chinese compared with Malay women amongst Asian ethnicities.
“This accords with an observational study in Singapore which showed lower conception rates in Malay compared with Chinese women (39 per cent vs. 46 per cent) over one year,” said the researchers.
Known as the Nutritional Intervention Preconception and During Pregnancy to Maintain Healthy Glucose Metabolism and Offspring Health (NiPPeR) trial, the researchers had previously published other findings from the trial, such as how the intervention could reduce preterm birth.
Source: Fertility and Sterility
NiPPeR Study Group, Time-to-conception and clinical pregnancy rate with a myo-inositol, probiotics and micronutrient supplement: secondary outcomes of the NiPPeR Randomized Trial
https://doi.org/10.1016/j.fertnstert.2023.01.047
Authors: Chan S-Y et al
