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.

Exercise prior to assisted fertilization in overweight and obese women (FertilEX): study protocol for a randomized controlled trial.

BACKGROUND: Overweight and obese women show reduced conception rates compared to women of normal weight. Insulin resistance and increased amount of visceral fat may be important mechanisms for reduced fertility in these women. Exercise training, in particular with high intensity, has previously been found to improve insulin sensitivity in overweight subjects. This study will assess if regular high-intensity interval training will improve the pregnancy rate after assisted fertilization compared to usual care only in overweight and obese women. We hypothesize that the intervention will improve pregnancy rate and insulin sensitivity compared to the control group. METHODS/DESIGN: The FertilEX study is a randomized, controlled trial in which 140 women with body mass index (BMI) >25 kg/m(2) accepted for assisted fertilization will be randomized (1:1) to an intervention group or a control group. The intervention group will do high-intensity interval training three times per week for 10 weeks before assisted fertilization. The control group will receive standard care assisted fertilization only. The primary outcome measure is ongoing pregnancy 7-8 weeks after embryo transfer. Secondary outcome measures are insulin sensitivity, peak oxygen uptake, brachial flow-mediated endothelial function, levels of reproductive hormones, and body composition. DISCUSSION: The results of this trial will provide knowledge about the effects of high-intensity exercise before assisted fertilization in subfertile overweight/obese women. If the intervention leads to beneficial effects on outcome measures, such programs should be considered as part of regular fertility care procedures for this population of women. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01933633 . Registered on 28 August 2013.

Possible metformin effect on adrenal androgens during pretreatment and IVF cycle in women with polycystic ovary syndrome.

OBJECTIVE: To determine the effects of metformin treatment on serum androgen levels ahead of and during the IVF cycle in infertile polycystic ovary syndrome (PCOS) women. DESIGN: A prospective, double-blind, placebo-controlled study. SETTING: Single-center, university IVF clinic. PATIENTS: Sixty-three PCOS women. INTERVENTION(S): Treatment with metformin 2,000 mg/day or identical placebo tablets for at least 14 weeks before and then during IVF treatment, ending on the day of hCG injection. MAIN OUTCOME MEASURE(S): Serum levels of dehydroepiandrosterone, dehydroepiandrosterone sulphate (DHEAS), androstenedione, free testosterone index (FTI), dihydrotestosterone, and the androgen metabolite 5alpha-androstane-3alpha, 17beta-diol-glucuronide were measured at five time points ending on the day of ovum collection. RESULT(S): During metformin pretreatment DHEAS increased, wheres other androgens were unaffected. During the IVF procedure androgens were unaffected by metformin treatment. Within 36 hours after the study medication was withdrawn the levels of androstenedione and FTI increased in the metformin group, whereas DHEAS decreased. CONCLUSION(S): In infertile PCOS women metformin treatment increased DHEAS levels. During the IVF cycle androgen levels were unaffected by metformin, whereas there was a "rebound" effect when stopping metformin treatment.

C-reactive protein levels are unaffected by metformin during pretreatment and an IVF cycle in women with polycystic ovary syndrome.

OBJECTIVE: Low-grade chronic inflammation, evaluated by serum C-reactive protein (CRP) levels, has been connected with the polycystic ovary syndrome (PCOS). Effects of metformin on CRP before and during IVF treatment in women with PCOS are unknown. DESIGN: A prospective double-blind placebo-controlled study. SETTING: Single-center IVF clinic. PATIENT(S): Sixty-three PCOS women. INTERVENTION(S): Treatment with 2000 mg/day metformin or identical placebo tablets for at least 14 weeks before and then during IVF treatment, ending on the day of hCG injection. MAIN OUTCOME MEASURE(S): The CRP levels at five time points ending on the day of ovum collection. RESULT(S): At inclusion of infertile untreated PCOS women, body mass index associated with CRP in multivariable regression analysis (r = 0.18). Androgen levels did not associate with CRP levels. Metformin did not influence CRP levels during pretreatment or IVF cycle. After hCG injection, CRP increased in both the metformin and the placebo groups with no significant difference between the groups. CONCLUSION(S): In infertile PCOS women, CRP levels are unaffected by metformin treatment. The CRP level increases during IVF treatment, and this increase is unaffected by concomitant metformin. We observed an association between CRP levels and body mass index.

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.

[Elective single embryo transfer in assisted reproduction]. / Tilbakeføring av ett embryo ved assistert befruktning.

BACKGROUND: More than one embryo is normally transferred per cycle to increase the probability for pregnancy after assisted reproduction. This has led to a high rate of multiple pregnancies, which increases the risk of complications for the mother and child. MATERIAL AND METHODS: 2765 assisted reproduction cycles were performed in the Fertility Unit at St. Olav's Hospital, Trondheim from 2002 to 2005. During this period we changed our cryopreservation programme and introduced elective single embryo transfer in an increasing number of women. RESULTS AND INTERPRETATION: From 2002 to 2005 the multiple pregnancy rate following transfer of fresh embryos decreased from 36 to 8 %. 75 % of all women who received hormone stimulated treatment with transfer of fresh embryos in 2005, had one embryo transferred. The proportion of cycles with surplus embryos available for cryopreservation increased from 27 % in 2002 to 69 % in 2005. Despite a slight reduction in the number of pregnancies during this period the pregnancy rate per oocyte recovery has remained stable. The improvement of our freezing/thawing routines has been crucial for improving treatment at the same time as we have reduced the fraction of multiple pregnancies. This implies less constraint on the couple and reduced costs for society. Lack of refund and valuation of freezing/thawing of embryos renders a continued optimal medical practice difficult.

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. METHODS: Eighty women aged between 18 and 40 years with PCOS were investigated in a prospective study. The inclusion criteria were polycystic ovaries (PCO), body mass index (BMI) >25 kg/m(2) and at least one of the following: testosterone >2.5 nmol/L, sex hormone binding globulin (SHBG) <30 nmol/L, fasting C-peptide >1.0 nmol/L, oligoamenorrhea or hirsutism. RESULTS: Eumenorrhoic and oligoamenorrhoic women with PCOS did not differ in age, age at menarche, blood pressure, BMI, free testosterone index (FTI), insulin C-peptide or fasting glucose. A thicker endometrium and a smaller ovarian volume were found in eumenorrhoic compared to oligoamenorrhoic patients. There was linear association between BMI and the number of diagnostic criteria met. CONCLUSION: BMI was associated with the severity of the PCOS. There were no differences in basic clinical and biochemical parameters between eumenorrhoic and oligoamenorrhoic patients with PCOS.

Dexamethasone reduces androgen levels in metformin-treated patients with polycystic ovary syndrome.

Women with polycystic ovary syndrome treated with metformin and lifestyle advice were studied. Additional treatment with dexamethasone, but not with bromocriptine, further reduced circulating androgen levels.