Thomas Åbyholm

Obesity is a risk factor for early pregnancy loss after IVF or ICSI

Background. Experience with polycystic ovary syndrome shows that insulin resistance is related to early pregnancy loss. This association was examined by comparing pregnancy outcome in obese and lean women.

Body weight, hyperinsulinemia, and gonadotropin levels in the polycystic ovarian syndrome: evidence of two distinct populations

OBJECTIVE To investigate the impact of body weight (BW) and insulin levels on gonadotropin and androgen levels in women with the polycystic ovarian syndrome (PCOS). DESIGN Comparative study of endocrinologic parameters in PCOS women. SETTING University Hospital Reproductive Endocrinology Unit. PATIENTS Thirty obese and 19 nonobese women with PCOS. Seven obese and 7 nonobese normal women. MAIN OUTCOME MEASURES Serum concentrations of insulin, testosterone, androstenedione, luteinizing hormone (LH), follicle-stimulating hormone. Serum LH response to gonadotropin-releasing hormone (GnRH) administration and assessment of insulin resistance by the continuous infusion of glucose with model assessment (CIGMA) test. RESULTS Fasting insulin levels correlated with body mass index (BMI). Basal LH levels correlated inversely with BMI. Nonobese women with PCOS had a higher LH response to GnRH than obese women with PCOS. Only obese women with PCOS showed insulin resistance and fasting hyperinsulinemia. CONCLUSIONS The data suggest that women with PCOS may be divided into two subgroups: those with obesity, insulin resistance, hyperinsulinemia, and normal/minimally elevated LH levels and those with normal BW, elevated LH levels, and normoinsulinemia.

Obstetric outcome in singleton pregnancies after assisted reproduction

Objective To compare the obstetric outcome of singleton pregnancies after various procedures of assisted reproduction with a control group. Methods Maternal and perinatal outcome in 355 assisted-reproduction singleton pregnancies (study group) with a duration of 140 days or more were compared retrospectively with a control group matched for age and parity. All assisted-reproduction pregnancies resulted from treatment in one university hospital, and all control subjects delivered in the obstetric department of the same hospital. The controls consisted of 643 women, also with singleton pregnancies, who were matched for age and parity. Results In the study group, the frequencies of pregnancy-induced hypertension and placenta previa were increased. More patients in the study group were delivered by elective cesarean. Pregnancies after assisted reproduction were of shorter duration, with an increased incidence of preterm birth. Infants in the study group had a lower mean birth weight than did those in the control group and were more frequently referred to a neonatal care unit. Conclusion Singleton pregnancies resulting from assisted reproduction represent obstetric risk cases, and the patients should be offered special attention during the pregnancy, which will probably be their only one.

Impact of Insulin Resistance on Pregnancy Complications and Outcome in Women with Polycystic Ovary Syndrome

The aim of the study was to determine the risk of developing gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH)/pre-eclampsia in a cohort of pregnant women with the polycystic ovary syndrome (PCOS) and known insulin sensitivity status. Pregnancies and neonatal outcome were recorded in a prospective cohort study comprising 29 non-insulin-resistant PCOS women, 23 insulin-resistant PCOS women and a control group of 355 women who had conceived after assisted reproduction. Hypertension, pre-eclampsia and GDM were recorded as well as pregnancy duration, method of delivery and birth weight. The frequency of hypertension was significantly elevated in PCOS women (11.5%) compared to controls (0.3%), p < 0.01. However, the frequency of pre-eclampsia was significantly elevated only in the insulin resistant PCOS women (13.5%) compared to controls (7.0%), p < 0.02. GDM was significantly more frequent in PCOS women (7.7%) than controls (0.6%), p < 0.01. Insulin resistance prior to pregnancy, determined by continuous infusion of glucose with model assessment (CIGMA) test, did not further increase the frequency of GDM. Newborns from PCOS pregnancies were significantly more often delivered by Caesarean section than controls (40.3 vs. 27.3%, p < 0.05) and transferred to neonatal intensive care unit more often than controls (19.2 vs. 9.0%, p < 0.01). Thus we show that the frequencies of pre-eclampsia and GDM are increased in PCOS pregnancies.

Prediction of response to controlled ovarian hyperstimulation: a comparison of basal and clomiphene citrate-stimulated follicle-stimulating hormone levels

OBJECTIVE To test the ovarian reserve in a high-risk population before controlled ovarian hyperstimulation for in vitro fertilization (IVF). DESIGN A prospective study comparing the outcome of a clomiphene citrate (CC) challenge test to the outcome of subsequent IVF cycles. SETTING Unit for assisted reproductive technology in a university hospital. PATIENTS, PARTICIPANTS Ninety-one infertile women with an age of 35 years or more, who had previous ovarian surgery or who had been diagnosed with ovarian endometriosis. MAIN OUTCOME MEASURE Relate follicle-stimulating hormone (FSH) levels before and after CC to frequency of cancellation of an IVF cycle because of a poor follicular response. RESULTS Twenty-one patients had elevated basal levels of FSH. Thirty-seven patients, including 20 with high basal levels, showed an excessive FSH response to CC with an FSH level after CC above the 95% confidence limit. Clomiphene citrate-stimulated FSH levels correlated better than basal levels with response to controlled ovarian hyperstimulation. An excessive FSH response to CC predicted a poor response outcome of subsequent controlled ovarian hyperstimulation for IVF with 85% accuracy. CONCLUSION Follicle-stimulating hormone response to CC predicts subsequent follicular response to controlled ovarian hyperstimulation.

In vitro fertilization is a successful treatment in endometriosis-associated infertility

OBJECTIVE To assess success rates of IVF and intracytoplasmic sperm injection in women with various stages of endometriosis. DESIGN Retrospective cohort study. SETTING Reproductive medicine unit in a university hospital. PATIENT(S) Infertile women (n = 2,245) with various stages of endometriosis or tubal factor infertility. INTERVENTION(S) IVF or intracytoplasmic sperm injection. MAIN OUTCOME MEASURE(S) Dose of FSH, number of oocytes retrieved, fertilization rate, implantation rate, pregnancy rate (PR), live birth/ongoing PR. RESULT(S) Women with endometriosis had similar pregnancy and live birth/ongoing PR as did women with tubal factor infertility, but the American Society for Reproductive Medicine (ASRM) stage I and II endometriosis patients had a lower fertilization rate, and stage III and IV patients required more FSH and had fewer oocytes retrieved. Splitting the stage III and IV groups into patients with and without endometriomas showed that the endometrioma group required more FSH and had a significantly lower pregnancy and live birth/ongoing PR. CONCLUSION(S) With the exception of patients with endometrioma, infertile women with various stages of endometriosis have the same success rates with IVF and intracytoplasmic sperm injection as patients with tubal factor. This contrasts with the systematic review on which the European Society of Human Reproduction and Embryology bases its recommendations.

In vitro fertilization/embryo transfer in unexplained infertility and minimal peritoneal endometriosis

Background. To compare the outcome of in vitro fertilization /embryo transfer (IVF‐ET) in unexplained infertility and infertility associated with minimal peritoneal endometriosis.

Complete surgical removal of minimal and mild endometriosis improves outcome of subsequent IVF/ICSI treatment

Surgical eradication of minimal and mild endometriosis has been shown to increase the birth rate both spontaneously and after intrauterine insemination. This study from a reproductive medicine unit at a referral university hospital examined whether surgical eradication of minimal and mild endometriosis prior to IVF improved the treatment outcome. Records of infertile patients with minimal and mild endometriosis (American Society for Reproductive Medicine stages I and II) with no prior IVF/intracytoplasmic sperm injection (ICSI) treatments were analysed. During the first treatment cycle, women who had undergone complete removal (n=399) of endometriotic lesions experienced, compared with women with diagnostic laparoscopy only (n=262), a significantly improved implantation rate (30.9% versus 23.9%, P=0.02), pregnancy rate (40.1% versus 29.4%, P=0.004) and live-birth rate per ovum retrieval (27.7% versus 20.6%, P=0.04). Surgical removal of minimal and mild endometriotic lesions also gave shorter time to first pregnancy and a higher cumulative pregnancy rate. The study shows that women with stages I and II endometriosis undergoing IVF/ICSI have significantly shorter time to pregnancy and higher live-birth rate if all visible endometriosis is completely eliminated at the time of diagnostic surgery. Surgical elimination of minimal and mild endometriosis has been shown to increase the birth rate both spontaneously and after intrauterine insemination. In this study from a reproductive medicine unit at a referral university hospital, we examined whether surgical elimination of minimal and mild endometriosis prior to IVF improved the outcome of this treatment as well. During the first IVF treatment cycle, women who had undergone complete surgical removal of endometriosis experienced, compared with women who still had their endometriosis, an improved rate of embryo implantation, pregnancy rate and live birth rate per ovum retrieval. Surgical removal of minimal and mild endometriotic lesions also gave shorter time to first pregnancy and a higher cumulative pregnancy rate. In summary, our study shows that women with minimal and mild endometriosis undergoing IVF have shorter time to pregnancy and higher live-birth rate if all visible endometriosis is completely eliminated before the start of treatment.

The effect of metformin on ovarian stimulation and in vitro fertilization in insulin-resistant women with polycystic ovary syndrome: an open-label randomized cross-over trial

Metformin effectively restores insulin sensitivity in insulin-resistant women with polycystic ovary syndrome (PCOS). We examined whether metformin ,given prior to and during ovarian stimulation for in vitro fertilization (IVF) ,altered follicle stimulating hormone (FSH) requirement and increased the number of collected oocytes in these women. Seventeen insulin-resistant women with PCOS were recruited to our IVF unit to receive two consecutive cycles of ovarian stimulation with or without metformin co-treatment ,the order of treatments being randomized using a table of random numbers. Metformin treatment (1500 mg/day) started 3 weeks before downregulation with buserelin acetate and was continued throughout ovarian stimulation with human recombinant FSH. Nine women completed both cycles ,the results of eight women being excluded because of pregnancy after the first cycle (n = 4) or because the protocol of the study was not followed (n = 4). Mean total FSH dose was 2301 IU (range 1500-6563 IU) in metformin cycles and 2174 IU (range 1200-3900 IU) in parallel control cycles ,while the mean number of collected oocytes was 8.6 (range 2-28) and 4.6 (range 1-16) ,respectively. Bayesian analysis showed probabilities of 0.05 that metformin reduces FSH requirement by at least 10% ,and of 0.61 that at least 10% more oocytes are collected after metformin co-treatment. Co-administration of metformin is therefore likely to increase the number of oocytes collected after ovarian stimulation in insulin-resistant women with PCOS but is unlikely to reduce the requirement for FSH.

Chemokines and Leukocyte Activation in the Fetal Circulation During Preeclampsia

Preeclampsia is a potentially life-threatening disease for both mother and fetus. Endothelial dysfunction is pivotal in the pathogenesis of this disorder, possibly reflecting a state of persistent inflammation. In the present study, we examined whether signs of inflammation with production of chemokines and leukocyte activation were present in the fetal circulation during preeclampsia. Venous cord blood was sampled during cesarean sections from 36 neonates born after uncomplicated pregnancies and from 35 born after severe preeclamptic pregnancies with premature newborns. The expression of adhesion molecules on neutrophils and monocytes was analyzed by flow cytometry, and plasma levels of chemokines and soluble adhesion molecules were analyzed by enzyme immunoassay. Newborns of preeclamptic mothers had increased expression of CD15s (P =0.003), CD49d/CD29 (P =0.01/0.005), and CD31 (P =0.007) on neutrophils and CD15s (P <0.001), CD11c (P =0.009), and CD54 (P =0.001) on monocytes. This activation of neutrophils and monocytes was accompanied by raised plasma levels of the CXC chemokines interleukin-8 (P =0.007) and growth-related oncogene-&agr; (P =0.01) and decreased plasma levels of soluble E-selectin (P =0.001) and L-selectin (P =0.002). Although raised levels of adhesion molecules on leukocytes or decreased levels of soluble adhesion molecules in plasma were not related to prematurity or the degree of preeclampsia, raised interleukin-8 levels were found only in neonates of preeclamptic mothers with the highest blood pressures. Our findings suggest the activation of neutrophils and monocytes in the fetus during preeclampsia involving enhanced chemokine activation, possibly contributing to the fetal morbidity of this disorder.