Kumar, P., & Khan, K. (2012). Effects of metformin use in pregnant patients with polycystic ovary syndrome. Journal of human reproductive sciences, 5(2), 166-169. https://doi.org/10.4103/0974-1208.101012
Kumar P, Khan K. Effects of metformin use in pregnant patients with polycystic ovary syndrome. J Hum Reprod Sci. 2012;5(2):166-169. doi:10.4103/0974-1208.101012
Kumar, Pratap, and Kashif Khan. "Effects of metformin use in pregnant patients with polycystic ovary syndrome." Journal of human reproductive sciences, vol. 5, no. 2, 2012, pp. 166-169.
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Metformin through PCOS pregnancy linked to fewer early losses
Women with PCOS who kept taking metformin through pregnancy had fewer early pregnancy losses in several studies. A 2012 review collects these reports. Several were case-controlled or cohort studies. One placebo-controlled trial of 257 women saw no drop in complications.
Key Findings
In a 3-year case-controlled study of 197 pregnant women with PCOS, women who continued metformin throughout pregnancy had significantly fewer early pregnancy losses than women who stopped after the first trimester.
In a prospective cohort of 360 non-diabetic women with PCOS, 200 continued metformin throughout pregnancy and 160 stopped. The continuing group had significantly less gestational diabetes.
In a case-controlled study of 137 women with PCOS split into 3 groups, the group that continued metformin throughout pregnancy had less fetal growth restriction, less preterm labor and more live births.
A randomized, placebo-controlled, double blind study of 257 pregnant women with PCOS, given metformin or placebo from first trimester to delivery, found no reduction in gestational diabetes, pre-eclampsia or preterm delivery.
Pooling 17 randomized controlled trials, a meta-analysis found no reduction in miscarriage risk in women with PCOS who took metformin before conception.
Interpretation
The paper is a narrative review of published studies in women with PCOS, now called PMOS (Polyendocrine Metabolic Ovarian Syndrome). The text does not say how studies were chosen, and it does not pool their results. The reports of fewer losses and less gestational diabetes come from case-controlled and cohort studies. Those designs do not assign treatment at random, so they can show association only. The placebo-controlled trial found no reduction in complications. The meta-analysis of randomized trials found no reduction in miscarriage risk with metformin before conception. The authors state that no definite guidelines recommend metformin for pregnant women with PCOS and that further research is necessary.
RRM Context
The review says high insulin may play a central role in PCOS. Insulin raises the ovaries' output of androgens. Restorative reproductive medicine looks for causes like this and treats them before conception.
Our editorial summary of this paper, not the article's abstract.
Abstract
Use of metformin throughout pregnancy in women with polycystic ovary syndrome (PCOS) has shown to reduce the rates of early pregnancy loss, preterm labor, and prevention of fetal growth restriction. Metformin has been shown to have encouraging effects on several metabolic aspects of polycystic ovarian syndrome, such as insulin sensitivity, plasma glucose concentration and lipid profile and since women with PCOS are more likely than healthy women to suffer from pregnancy-related problems like early pregnancy loss, gestational diabetes mellitus and hypertensive states in pregnancy, the use of metformin therapy in these patients throughout pregnancy may have beneficial effects on early pregnancy loss and development of gestational diabetes.
Bhat P et al., 2025·Journal of assisted reproduction and genetics·Free full text on PubMed Central
Congenital anomalies (CAs) are a leading cause of perinatal and child mortality. With the increasing use of assisted reproductive technology (ART), there is a growing need for research on the health outcomes of children conceived through ART. This systematic review was performed to assess the incidence of CAs in ART-conceived children compared to those conceived naturally. This review followed the PRISMA 2020 guidelines and was registered with PROSPERO. A total of 113 studies were included in this meta-analysis, comprising 768,929 children in the ART group and 40,709,337 children in the control group which comprised spontaneously conceived (SC) children. The primary findings indicated that ART-conceived children have a marginally higher risk of CAs compared to the control group. Subgroup analyses showed that children conceived via ICSI, Day 3 transfer, and fresh embryo transfer (ET) had a slightly higher risk of CAs than those conceived via IVF, Day 5 transfer, or frozen embryo transfer (FET). The study highlights a slightly increased incidence of CAs among ART-conceived children over SC children, underscoring the importance of improving ART methods and closely monitoring the health of these children to reduce the risk of CAs.
Saha A et al., 2018·J Lab Physicians·Free full text on PubMed Central
Well-differentiated papillary mesothelioma is a rare tumor occurring predominantly in the peritoneum of young women, a few with history of asbestos exposure. A 28-year-old woman presented with ascites and pain abdomen. Ultrasonography and computed tomography scan of the abdomen revealed a mass in the retroperitoneum measuring 15 cm × 12 cm. Histopathological examination along with immunohistochemistry (IHC) confirmed it to be a papillary mesothelioma in the peritoneum. It is difficult to differentiate from more common malignant mesothelioma and papillary adenocarcinoma, which also have poorer prognosis. The difficulty can be resolved by clinico-radiological correlation along with histopathological examination and IHC.
Carter ND et al., 2002·CMAJ·Free full text on PubMed Central
Exercise programs improve balance, strength and agility in elderly people and thus may prevent falls. However, specific exercise programs that might be widely used in the community and that might be "prescribed" by physicians, especially for patients with osteoporosis, have not been evaluated. We conducted a randomized controlled trial of such a program designed specifically for women with osteoporosis. We identified women 65 to 75 years of age in whom osteoporosis had been diagnosed by dual-energy X-ray absorptiometry in our hospital between 1996 and 2000 and who were not engaged in regular weekly programs of moderate or hard exercise. Women who agreed to participate were randomly assigned to participate in a twice-weekly exercise class or to not participate in the class. We measured baseline data and, 20 weeks later, changes in static balance (by dynamic posturography), dynamic balance (by a timed figure-eight run) and knee extension strength (by dynamometry). Of 93 women who began the trial, 80 completed it. Before adjustment for covariates, the intervention group tended to have greater, although nonsignificant, improvements in static balance (mean difference 4.8%, 95% confidence interval [CI] -1.3% to 11.0%), dynamic balance (mean difference 3.3%, 95% CI -1.7% to 8.4%) and knee extension strength (mean difference 7.8%, 95% CI -5.4% to 21.0%). Mean crude changes in the static balance score were -0.85 (95% CI -2.91 to 1.21) for the control group and 1.40 (95% CI -0.66 to 3.46) for the intervention group. Mean crude changes in figure-eight velocity (dynamic balance) were 0.08 (95% CI 0.02 to 0.14) m/s for the control group and 0.14 (95% CI 0.08 to 0.20) m/s for the intervention group. For knee extension strength, mean changes were -0.58 (95% CI -3.02 to 1.81) kg/m for the control group and 1.03 (95% CI -1.31 to 3.34) kg/m for the intervention group. After adjustment for age, physical activity and years of estrogen use, the improvement in dynamic balance was 4.9% greater for the intervention group than for the control group (p = 0.044). After adjustment for physical activity, cognitive status and number of fractures ever, the improvement in knee extension strength was 12.8% greater for the intervention group than for the control group (p = 0.047). The intervention group also had a 6.3% greater improvement in static balance after adjustment for rheumatoid arthritis and osteoarthritis, but this difference was not significant (p = 0.06). Interpretation: Relative to controls, participants in the exercise program experienced improvements in dynamic balance and strength, both important determinants of risk for falls, particularly in older women with osteoporosis.
Carter ND et al., 2001·Br J Sports Med·Free full text on PubMed Central
To test the efficacy of a community based 10 week exercise intervention to reduce fall risk factors in women with osteoporosis. Static balance was measured by computerised dynamic posturography (Equitest), dynamic balance by timed figure of eight run, and knee extension strength by dynamometry. Subjects were randomised to exercise intervention (twice weekly Osteofit classes for 10 weeks) or control groups. The outcome in 79 participants (39 exercise, 40 control) who were available for measurement 10 weeks after baseline measurement is reported. After confounding factors had been controlled for, the exercise group did not make significant gains compared with their control counterparts, although there were consistent trends toward greater improvement in all three primary outcome measures. Relative to the change in control subjects, the exercise group improved by 2.3% in static balance, 1.9% in dynamic balance, and 13.9% in knee extension strength. A 10 week community based physical activity intervention did not significantly reduce fall risk factors in women with osteoporosis. However, trends toward improvement in key independent risk factors for falling suggest that a study with greater power may show that these variables can be improved to a level that reaches statistical significance.
Related research
Metabolic and Endocrine Agents · Insulin Sensitizing Agents
To assess whether metformin safely reduced development of gestational diabetes in women with the polycystic ovary syndrome (PCOS). Prospective and retrospective study. Outpatient clinical research center. PATIENT(S): The prospective study included 33 nondiabetic women with PCOS who conceived while taking metformin and had live births; of these, 28 were taking metformin through delivery. The retrospective study included 39 nondiabetic women with PCOS who had live birth pregnancies without metformin therapy. INTERVENTION(S): Metformin, 2.55 g/d, throughout pregnancy in women with PCOS. MAIN OUTCOME MEASURE(S): Development of gestational diabetes in women with PCOS. RESULT(S): Before metformin therapy, after covariance adjustment for age, the two cohorts did not differ in height, weight, basal metabolic index, insulin, insulin resistance, or insulin secretion. Both cohorts had high fasting insulin, were insulin resistant, and had high insulin secretion. Among the 33 women who received metformin, gestational diabetes developed in 1 of 33 (3%) pregnancies versus 8 of 12 (67%) of their previous pregnancies without metformin. Among the 39 women who did not take metformin, gestational diabetes developed in 14 of 60 (23%) pregnancies. When all live births were combined, gestational diabetes occurred in 22 of 72 pregnancies (31%) in women who did not take metformin versus 1 of 33 pregnancies (3%) in those who took metformin. With gestational diabetes as the response variable and age at delivery and treatment group (metformin or no metformin) as explanatory variables, the odds ratio for gestational diabetes in women with metformin versus without metformin was 0.093 (95% CI: 0.011 to 0.795). With gestational diabetes in 93 pregnancies as the response variable and age at delivery and treatment group (metformin no metformin) as explanatory variables, the odds ratio of gestational diabetes in pregnancies in women taking metformin versus without metformin was 0.115 (95% CI: 0.014 to 0.938). CONCLUSION(S): In PCOS, use of metformin is associated with a 10-fold reduction in gestational diabetes (31% to 3%). It also reduces insulin resistance and insulin secretion, thus decreasing the secretory demands imposed on pancreatic beta-cells by insulin resistance and pregnancy.
Metabolic and Endocrine Agents · Insulin Sensitizing Agents
Women with polycystic ovary syndrome (PCOS) are considered to be at increased risk of miscarriage. Since metformin has beneficial effects on the risk factors contributing to first-trimester abortion in PCOS patients, we hypothesized that metformin - owing to its metabolic, endocrine, vascular and anti-inflammatory effects - may reduce the incidence of first-trimester abortion in PCOS women. A prospective cohort study was set up to determine the beneficial effects of metformin on PCOS patients during pregnancy. Two hundred non-diabetic PCOS patients were evaluated while undergoing assisted reproduction. One hundred and twenty patients became pregnant while taking metformin, and continued taking metformin at a dose of 1000-2000 mg daily throughout pregnancy. Eighty women who discontinued metformin use at the time of conception or during pregnancy comprised the control group. Both groups were similar with respect to all background characteristics (age, body mass index, waist/hip ratio, follicle-stimulating hormone, luteinizing hormone, estradiol and dehydroepiandrosterone sulfate levels). Rates of early pregnancy loss in the metformin group were 11.6% compared with 36.3% in the control group (p < 0.0001; odds ratio = 0.23, 95% confidence interval 0.11-0.42). Administration of metformin throughout pregnancy to women with PCOS was associated with a marked and significant reduction in the rate of early pregnancy loss.
Metabolic and Endocrine Agents · Insulin Sensitizing Agents
To determine whether metformin would safely reduce the rate of first-trimester spontaneous abortion without teratogenicity in 19 women with the polycystic ovary syndrome (PCOS). Prospective pilot study. Outpatient. PATIENT(S): Twenty-two previously oligoamenorrheic, nondiabetic women with PCOS; 125 women with PCOS who were not currently pregnant and who had > or = 1 previous pregnancy while they were not receiving metformin. INTERVENTION(S): Metformin, 1.5-2.55 g/day, throughout pregnancy. MAIN OUTCOME MEASURE(S): Rates of first-trimester spontaneous abortion and teratogenicity. RESULT(S): Before metformin, 10 women had 22 previous pregnancies with 16 first-trimester spontaneous abortions (73%). While receiving metformin, these 10 women had 6 normal live births (60%), 1 spontaneous abortion (10%), and 3 normal ongoing pregnancies (30%) (all > or = 13 weeks; median gestation, 23 weeks). Among women receiving metformin, including those with live births and normal pregnancy for at least the first trimester, 1 of 10 (10%) had first-trimester spontaneous abortion compared with 73% in 22 previous pregnancies without metformin (P<.002). To date, the 19 women receiving metformin have had no adverse maternal side effects, and no birth defects have occurred; 9 (47%) had normal term live births, 2 (11%) had normal and appropriate for gestational age births (one at 33 and one at 35 weeks), 6 (32%) have ongoing normal pregnancies lasting longer than the first trimester, and 2 (10.5%) had first-trimester spontaneous abortions. Sonography showed normal fetal development without congenital defects in the 6 ongoing pregnancies (median gestation, 23 weeks). Among women who received metformin before conception, reductions in insulin and plasminogen activator inhibitor activity were correlated (r=0.65, P=.04). CONCLUSION(S): Metformin therapy throughout pregnancy in women with PCOS reduces the otherwise high rate of first-trimester spontaneous abortion seen among women not receiving metformin and does not appear to be teratogenic.
Metabolic and Endocrine Agents · Insulin Sensitizing Agents
Insulin resistance is a prominent feature of polycystic ovarian syndrome (PCOS), and women with the disorder are at increased risk for the development of other diseases that have been linked to insulin resistance-namely, type 2 diabetes and cardiovascular disease. This association between insulin resistance and PCOS must guide the chronic management of the disorder, and accumulating evidence suggests that administration of insulin-sensitizing drugs to individuals at high risk for type 2 diabetes decreases the rate of conversion to overt disease. In contrast, limited evidence exists to suggest that oral contraceptive pills-the currently standard therapy for PCOS-may actually decrease insulin sensitivity and induce impaired glucose tolerance in women with PCOS. Hence, PCOS should be regarded as a general health issue and the use of insulin-sensitizing drugs such as metformin should be considered for the prevention of type 2 diabetes.
PMID 23162354 23162354 DOI 10.4103/0974-1208.101012 10.4103/0974-1208.101012 Kumar et al. 2012, Kumar 2012
Cite this article
Kumar, P., & Khan, K. (2012). Effects of metformin use in pregnant patients with polycystic ovary syndrome. Journal of human reproductive sciences, 5(2), 166-169. https://doi.org/10.4103/0974-1208.101012
Kumar P, Khan K. Effects of metformin use in pregnant patients with polycystic ovary syndrome. J Hum Reprod Sci. 2012;5(2):166-169. doi:10.4103/0974-1208.101012
Kumar, Pratap, and Kashif Khan. "Effects of metformin use in pregnant patients with polycystic ovary syndrome." Journal of human reproductive sciences, vol. 5, no. 2, 2012, pp. 166-169.
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