Perinatal outcome of children born after frozen and fresh embryo transfer: the Finnish cohort study 1995-2006.

BACKGROUND: The number of children born after frozen embryo transfer (FET) is steadily rising. However, studies on obstetric and perinatal outcomes are limited. Our primary aim was to compare the perinatal health of children born after FET and fresh embryo transfer, and to use data from children born after spontaneous conception as a reference. METHODS: In a register-based cohort study we evaluated the obstetric and perinatal outcomes of children born after FET (n = 2293), fresh embryo transfer (n = 4151) and those born after spontaneous pregnancy (reference group; n = 31 946). Data were collected from the registers of two infertility outpatient clinics, two university hospitals and the Finnish Medical Birth Register (1995-2006). RESULTS: After adjusting for confounding factors the FET group showed decreased risks of preterm birth [adjusted odd ratio (AOR) 0.83, 95% confidence interval (CI) 0.71-0.97], low birthweight (AOR 0.74; 0.62-0.88) and being small for gestational age (AOR 0.63; 0.49-0.83) compared with the fresh embryo transfer group. Mean birthweight was 134 g higher in the FET singletons versus the fresh embryo transfer singletons (P< 0.0001). When FET singletons were compared with the reference group, increased risks of preterm birth (AOR 1.45; 1.25-1.68) and low birthweight (AOR 1.22; 1.03-1.45) and a decreased risk of being small for gestational age (AOR 0.71; 0.54-0.92) were found. No excess of perinatal and infant mortality occurred between the groups. CONCLUSIONS: Embryo freezing does not adversely affect perinatal outcome in terms of prematurity, low birthweight and being small for gestational age versus the fresh embryo transfer and the outcome is similar or even better, particularly regarding fetal growth. Our study, which is one of the largest on FET pregnancies, provides further evidence on the safety of FET.

Ovulation side and cycle fecundity: a retrospective analysis of frozen/thawed embryo transfer cycles.

The aim of the study was to evaluate a possible lateral difference in ovarian activity and its effect on cycle fecundity. A database was analysed retrospectively which covered 477 cycles in which frozen/thawed embryo transfer had been carried out. The cycles were spontaneous, with no hormonal treatment. Women with ovulation problems as a reason for infertility treatment were excluded. Factors investigated were the side of ovulation, endometrial thickness on cycle days 10-12 and on the day of embryo transfer, and pregnancy rate per embryo transfer. Ovulation was right-sided in 273 of the 477 cycles (57.2%) and left-sided in 204 of the cycles (42. 8%) (95% CI 38.3-47.2, P = 0.002). In the age category of 30-37 years, covering 288 cycles, the incidence of left-sided ovulation was 126 (43.7%, 95% CI 38.0-49.5, P = 0.034). In this category, the endometrial thickness (+/-SD) was significantly greater on the day of embryo transfer (i.e. at time of implantation) when there had been left-sided ovulation compared with right-sided [9.6 mm (2.0) versus 9.1 mm (1.8), P = 0.037]. In addition, the pregnancy rate per embryo transfer was higher when ovulation had been on the left side [32/126 (25.2%) versus right side 24/162 (14.8%), P = 0.035, 95% CI 0.0122-0.199]. In conclusion, right-sided ovulation was more frequent than left-sided in the whole group. This is the first study to report that the side of ovulation has a clinical impact. These data support the hypothesis that the side of ovulation is significant in terms of embryo implantation.

Obstetric and perinatal outcome of pregnancies after intrauterine insemination.

The main aim of this study was to evaluate the obstetric and perinatal outcome of pregnancies after intrauterine insemination (IUI) with the partner's spermatozoa combined with ovarian stimulation. Information concerning the antenatal care and obstetric and perinatal outcome of IUI pregnancies (n = 111), spontaneous (n = 333) and in-vitro fertilization (IVF) (n = 333) was obtained from the Finnish Medical Birth Register (MBR). The multiple birth rate in the IUI group was 17% (19/111). Significantly less antenatal care was required by the IUI group than the IVF group. The frequency of Caesarean section was 25% for IUI singletons and 58% for IUI multiples, similar to the other groups. The mean (SD) gestational age for IUI singletons at birth was 39.5 (1.8) weeks, with a mean birth weight of 3285 (575) g, compared with 3448 (600) g in non-assisted singletons (P < 0.05). For IUI multiples the mean gestational age at birth was 36.0 (2.8) weeks and the mean birth weight was 2449 (678) g. The incidence of preterm birth, low birth weight or low Apgar scores and the need for neonatal care were similar in all groups. One case of major malformation and two perinatal deaths were recorded in the IUI group. In conclusion, IUI treatment did not appear to increase obstetric or perinatal risks compared with matched spontaneous or IVF pregnancies. Most problems were associated with patient characteristics and multiple pregnancy. Reduction of the high incidence of multiple pregnancies after assisted reproductive technology is essential to improve its outcome.

Intrauterine insemination treatment in subfertility: an analysis of factors affecting outcome.

A total of 811 intrauterine insemination (IUI) cycles in which clomiphene citrate/human menopausal gonadotrophin (HMG) was used for ovarian stimulation were analysed retrospectively to identify prognostic factors regarding treatment outcome. The overall pregnancy rate was 12.6% per cycle, the multiple pregnancy rate 13.7%, and the miscarriage rate 23.5%. Logistic regression analysis revealed five predictive variables as regards pregnancy: number of the treatment cycle (P = 0.009), duration of infertility (P = 0.017), age (P = 0.028), number of follicles (P = 0.031) and infertility aetiology (P = 0.045). The odds ratios for age < 40 years, unexplained infertility aetiology (versus endometriosis) and duration of infertility < or = 6 years were 3.24, 2.79 and 2.33, respectively. A multifollicular ovarian response to clomiphene citrate/HMG resulted in better treatment success than a monofollicular response, and 97% of the pregnancies were obtained in the first four treatment cycles. The results indicate that clomiphene citrate/HMG/IUI is a useful and cost-effective treatment option in women < 40 years of age with infertility duration < or = 6 years, who do not suffer from endometriosis.

Long gonadotrophin releasing hormone agonist/human menopausal gonadotrophin protocol for ovarian stimulation in intrauterine insemination treatment.

OBJECTIVE: This prospective study was undertaken to examine the usefulness of a long gonadotrophin releasing hormone agonist (GnRH-a)/human menopausal gonadotrophin (hMG) protocol in intrauterine insemination (IUI) treatment. The results were compared to those of clomiphene citrate (CC)/hMG/IUI. STUDY DESIGN: Seventy-five patients were recruited to a GnRH-a/hMG group (group 1) while 88 patients underwent CC/hMG stimulation and served as controls (group 2). The study subjects were stimulated with a long GnRH-a/hMG regimen. IUI was performed 36 h after the administration of human chorionic gonadotrophin. RESULTS: The number of preovulatory follicles, the thickness of endometrium and sperm parameters were similar in both groups. The hMG requirements were significantly higher in group 1 than in group 2 (21.2 +/- 5.1 vs. 8.1 +/- 3.1 ampoules). The pregnancy rate was 20% in group 1 and 12.5% in group 2, the difference being not significant. CONCLUSION: The pregnancy rates were not significantly different between the GnRH-a/hMG/ IUI and CC/hMG/IUI groups. In addition, GnRH-a/hMG stimulation is notably more expensive than CC/hMG, and for these reasons, GnRH-a/hMG stimulation is not cost-effective in routine IUI therapy.

Comparison of fallopian tube sperm perfusion with intrauterine insemination in the treatment of infertility.

OBJECTIVE: To compare the efficacy of fallopian tube sperm perfusion utilizing a Foley catheter technique with standard IUI. DESIGN: Randomized controlled study. SETTING: The infertility units of the University Central Hospital and the Family Federation of Finland, Oulu, Finland. PATIENT(S): One hundred infertile women with unexplained factor, minimal to mild endometriosis, mild male factor, or ovarian dysfunction, undergoing 50 IUI and 50 fallopian tube sperm perfusion cycles stimulated by clomiphene citrate and hMG. INTERVENTION(S): Thirty-six hours after hCG administration, patients were randomized to either the IUI group (group 1, 50 patients and cycles) or the fallopian tube sperm perfusion group (group 2, 50 patients and cycles). Intrauterine insemination was performed using a standard method and fallopian tube sperm perfusion with a pediatric Foley catheter, which prevents the reflux of sperm suspension. MAIN OUTCOME MEASURE(S): Number of clinical pregnancies. RESULTS(S): The fallopian tube sperm perfusion method using a Foley catheter technique was easy to perform and convenient for the patients. The overall pregnancy rate per cycle was 8% for fallopian tube sperm perfusion and 20% for IUI, a difference that was not significant. CONCLUSION(S): The fallopian tube sperm perfusion method using a Foley catheter offers no advantage in comparison with the conventional IUI technique.

Insulin-like growth factors and their binding proteins in the venous effluents of ovary and adrenal gland in severely hyperandrogenic women.

Insulin and insulin-like growth factors (IGF) are thought to play an important role in the pathogenesis of excessive androgen production. To explore this question further we measured the concentrations of IGF-I and -II and their binding proteins (IGFBP-1 and-3) in adrenal and ovarian vein samples of severely hyperandrogenic women (serum testosterone > 5 nmol/l) collected as part of their diagnostic work-up. The concentration of IGF-II was slightly but not significantly higher in the ovarian vein than in the adrenal and peripheral veins. The concentrations of IGF-I and IGFBP were identical in both the adrenal and ovarian veins and did not differ from those in the peripheral circulation. The concentration of IGFBP-1 was negatively correlated (r = -0.60, P > 0.05) with insulin and IGFBP-3 showed a strong positive correlation with IGF-1 (r = 0.90, P > 0.01). These results indicate that neither the ovary nor the adrenal gland contributes significantly to the circulating pool of IGF or their binding proteins in severely hyperandrogenic subjects. Hyperinsulinaemia is associated with low circulating IGFBP-1 concentrations and IGFBP-3 seems to be an excellent indicator of the peripheral IGF-I concentration. The concentrations of IGF-I suggested decreased somatotrophic activity in these obese, hyperinsulinaemic subjects.

Pretreatment transvaginal ultrasound examination predicts ovarian responsiveness to gonadotrophins in in-vitro fertilization.

The objective of this study was to determine the predictive value of the number of follicles seen by transvaginal ultrasound before gonadotrophin stimulation on the ovarian responsiveness of 166 infertile women undergoing in-vitro fertilization (IVF) treatment. The main variables were patient age, ovarian volume and number of ovarian follicles measuring 2-5 mm on transvaginal ultrasound before gonadotrophin stimulation. Based on the sum of ovarian follicles in both ovaries the patients were divided into three groups of inactive (<5 follicles), normal (5-15 follicles) or polycystic (PCO)-like ovaries (>15 follicles). The main outcome measure was the number of recovered oocytes. The number of follicles was correlated more strongly with the number of recovered oocytes (r2 = 0.131; P = 0.0001) than age alone (r2 = -0.053; P = 0.005). Fewer oocytes were recovered from patients with inactive ovaries (5.4 +/- 2.5; P = 0.006) than with normal (7.5 +/- 4.5) or PCO-like ovaries (10.5 +/- 5.1). Ovarian volume was correlated with the number of follicles before stimulation (P = 0.0001), but not with the number of oocytes. The number of small follicles present before ovarian stimulation was a better predictor of the outcome than ovarian volume or age alone. Patients can be identified with inactive ovaries which will have a poor response to IVF treatment, a key factor for counselling couples and optimizing resources.

Adrenal steroidogenesis is related to insulin in hyperandrogenic women.

OBJECTIVE: To evaluate ovarian and adrenal steroid secretion in women with severe hyperandrogenism. DESIGN: A prospective study. SETTING: The Gynecological Endocrine Research Unit of the University Central Hospital, Oulu, Finland. PATIENTS: Thirteen obese, hirsute women with severe hyperandrogenism. INTERVENTIONS: Adrenocorticotropin hormone stimulation and dexamethasone suppression tests and selective catheterizations of the left ovarian and adrenal veins were performed. MAIN OUTCOME MEASURES: The concentrations of insulin, P, 17-hydroxyprogesterone (17-OHP), androstenedione (A), T, DHEA, DHEAS, and cortisol were measured. RESULTS: The secretory gradients of T and its precursors, P, 17-OHP, A, and DHEA in the selective catheterizations showed the adrenal to be the main source of excessive steroid production in these patients. The concentrations of P (r = 0.82), 17-OHP (r = 0.89), A (r = 0.84), T (r = 0.86), and cortisol (r = 0.87) in the adrenal vein showed a strong correlation with insulin measured from the same samples. CONCLUSIONS: Excessive androgens were secreted mainly by the adrenals in these obese hyperinsulinemic women. Correlation analyses suggested that insulin stimulates adrenal androgen and cortisol secretion, which may constitute an important component of the pathogenetic mechanisms of hyperandrogenism and the polycystic ovary syndrome.

Intrafollicular insemination for the treatment of infertility.

The effectiveness of intrafollicular insemination (IFI) for the treatment of non-tubal infertility was investigated in a pilot study. A total of 50 infertility patients with normal tubal function verified by laparoscopy or hysterosalpingography were stimulated with clomiphene citrate/human menopausal gonadotrophin. Washed spermatozoa were injected into one to three pre-ovulatory follicles via vaginal puncture 12 or 30 h after human chorionic gonadotrophin administration. Natural progesterone was given for luteal support. The IFI procedure was technically very simple and convenient for the patient and no complications were recorded. One normal intra-uterine pregnancy resulted. The results indicate that by comparsion with other assisted reproductive technologies IFI is very inefficacious for treating non-tubal infertility. Our data suggest that the intrafollicular environment in the preovulatory period is not favourable for fertilization.