Sigrun Kjøtrød

Use of metformin before and during assisted reproductive technology in non-obese young infertile women with polycystic ovary syndrome: a prospective, randomized, double-blind, multi-centre study

BACKGROUND To study the effect of metformin before and during assisted reproductive technology (ART) on the clinical pregnancy rate (CPR) in non-obese women with polycystic ovary syndrome (PCOS). METHODS A multi-centre, prospective, randomized, double-blind study was conducted in eight IVF clinics in four Nordic countries. We enrolled 150 PCOS women with a body mass index <28 kg/m(2), and treated them with 2000 mg/day metformin or identical placebo tablets for ≥ 12 weeks prior to and during long protocol IVF or ICSI and until the day of pregnancy testing. The primary outcome measure was CPR. Secondary outcome measures included spontaneous pregnancy rates during the pretreatment period, and the live birth rate (LBR). RESULTS Among IVF treated women (n = 112), biochemical pregnancy rates were identical in both groups (42.9%), and there were no significant differences in the metformin versus the placebo group in CPR [39.3 versus 30.4%; 95% confidence interval (CI): -8.6 to 26.5]. The LBR was 37.5 versus 28.6% (95% CI: -8.4 to 26.3). However, prior to IVF there were 15 (20.3%) spontaneous pregnancies in the metformin group and eight (10.7%) in the placebo group (95% CI: -1.9 to 21.1; P = 0.1047). According to intention to treat analyses (n = 149); significantly higher overall CPR were observed in the metformin versus placebo group (50.0 versus 33.3%; 95% CI: -1.1 to 32.3; P = 0.0391). LBR was also significantly higher with use of metformin versus placebo (48.6 versus 32.0; 95% CI: 1.1 to 32.2; P = 0.0383). No major unexpected safety issues or multiple births were reported. More gastrointestinal side effects occurred in the metformin group (41 versus 12%; 95% CI: 0.15 to 0.42; P < 0.001). CONCLUSIONS Metformin treatment for 12 weeks before and during IVF or ICSI in non-obese women with PCOS significantly increases pregnancy and LBRs compared with placebo. However, there was no effect on the outcome of ART per se. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT00159575.

Homocysteine levels are unaffected by metformin treatment in both nonpregnant and pregnant women with polycystic ovary syndrome

Background. Women with polycystic ovary syndrome have elevated homocysteine levels. Elevated homocysteine levels associate with pregnancy complications. Women with polycystic ovary syndrome are often treated with metformin, a drug that may increase homocysteine levels. Hence, we investigated the effect of metformin treatment on homocysteine levels in nonpregnant and pregnant women with polycystic ovary syndrome. Methods. Two prospective randomized placebo‐controlled studies included women with polycystic ovary syndrome in a university hospital setting. Sixty‐three infertile women were treated with metformin 1,000 mg bid or placebo for 16 weeks and 38 pregnant women with metformin 850 mg bid or placebo from the first trimester and throughout pregnancy. All the women had polycystic ovary syndrome and all participants received diet and lifestyle advice, and oral folate and vitamin B12 substitution, and a daily oral multivitamin tablet. The main outcome measures were serum levels of homocysteine, folate, and vitamin B12. Results. Serum homocysteine levels were unaffected by metformin treatment both in nonpregnant and pregnant women with polycystic ovary syndrome. However, in nonpregnant women both serum folate and vitamin B12 levels decreased with treatment. At inclusion in nonpregnant women, serum homocysteine levels associated negatively with serum levels of folate and methyl malonic acid and positively with free testosterone index. No such associations were seen in pregnant women. Conclusions. Metformin treatment in women with polycystic ovary does not increase serum homocysteine levels in the nonpregnant or the pregnant state.

Clinical, biochemical and ultrasonographic characteristics of Scandinavian women with PCOS

Background.  The aim was to investigate the clinical, biochemical and ultrasonographic characteristics of Scandinavian women with polycystic ovarian syndrome (PCOS), and to see whether there were any differences between eumenorrhoic and oligoamenorrhoic women.

Women undergoing assisted fertilisation and high-intensity interval training: a pilot randomised controlled trial

Objectives Overweight and obese women often seek assisted fertilisation. In the obese population, pregnancy rates are 30%–75% below that of normal weight women who undergo assisted fertilisation. We hypothesised that high-intensity interval training (HIT) would improve fertility by improving insulin sensitivity and thus affect the hypothalamic-pituitary-ovarian axis and ovarian androgen production. Our aim was to assess whether HIT prior to assisted fertilisation would increase pregnancy rate. Methods Eighteen overweight and obese women (body mass index>25.0 kg/m2) were randomised to HIT (n=8) or usual care (control, n=10) before assisted fertilisation. HIT was undertaken three times weekly for 10 weeks; two sessions of 4×4 min HIT and one session of 10×1 min HIT. Primary outcome was ongoing pregnancy. Secondary outcomes included insulin sensitivity, reproductive hormones, oxygen uptake and body composition. Results Four women got pregnant in both the HIT group (50%) and in the control group (44%), no between-group difference (p=0.6). Insulin sensitivity (glucose infusion rate) improved significantly after HIT, from 264.1 mg/m2/min (95% CI 193.9 to 334.4) at baseline to 324.7 mg/m2/min (95% CI 247.2 to 402.2) after 10 weeks (between-group difference, p=0.04). Fasting glucose, visceral fat, waist circumference and VO2peak were significantly improved in the group that undertook HIT. Conclusions HIT significantly improved insulin sensitivity, VO2peak and abdominal fat. Low statistical power makes it difficult to conclude on whether HIT prior to assisted fertilisation could increase pregnancy rate. Larger trials are needed to determine if improvements in insulin sensitivity are clinically relevant for assisted fertilisation success rates in this population.