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Multiple pregnancies: risk factors and prognostic variables during induction of ovulation with human menopausal gonadotrophins.

Multiple pregnancies still constitute a major and relatively frequent complication of induction of ovulation by human menopausal gonadotrophins (HMG) despite the increasing sophistication of monitoring techniques. In order to define specific variables which may be associated with multiple pregnancies, we have compared 51 multiple pregnancy cycles to 51 consecutive control singleton pregnancy cycles, following HMG induction of ovulation. The aetiology and classification of anovulation, duration of infertility, total amount of HMG utilized per cycle and the duration of stimulation were not associated with an increase in the rate of multiple pregnancy. Basal serum oestradiol levels and its periovulatory pattern were remarkably similar in the singleton and multiple pregnancy groups. The mean age of the multiple pregnancy group (29.4 +/- 4.4 years) was significantly lower than the mean age of the singleton pregnancy group (31.6 +/- 5.3 years) (P less than 0.05). In the multiple pregnancy group, there were significantly more cycles with intermediate sized (15-17 mm). (P less than 0.002), small sized (12-14 mm). (P less than 0.02) and immature follicles (less than 12 mm) (P less than 0.03), at the time of human chorionic gonadotrophin (HCG) administration, as compared with the singleton pregnancy group. Furthermore, a direct linear correlation was observed between the number of intermediate sized follicles and number of implanted embryos. The presence of intermediate sized follicles at the time of HCG administration after HMG induction of follicular maturation is predictive of, and independently associated with, a higher incidence of multiple pregnancy.

Estradiol↗

New Belgian embryo transfer policy leads to sharp decrease in multiple pregnancy rate.

Since 1 July 2003, a new transfer policy aiming to reduce multiple pregnancies was brought into law in Belgium. The policy restricts the number of embryos transferred, depending on the patient's age and treatment cycle. This study aimed to evaluate the effect of this policy. Two 15-month periods before and after the start of the new law were compared for the following parameters: positive human chorionic gonadotrophin (HCG), clinical pregnancy rate and multiple pregnancy rate according to the age categories defined by the policy: <36, 36-39 and 40-42 years. HCG rates (34.2 and 32.8%) and clinical pregnancy rates (26.2 and 24.0%) per cycle were similar for the two periods. Overall, the multiple pregnancy rate was reduced from 29.1 to 9.5% (all patients) and from 28.9 to 6.2% in women <36 years. Most twins were observed in the third cycle of patients <36 years and in the first three cycles in women of 36-39 years. It can be concluded that a significant decline (P < 0.001) in multiple pregnancies was mainly observed in patients <36 years of age. Clinical pregnancy rates were not compromised by the new law. Elective single embryo transfer should be considered more seriously for women 36-39 years of age.

Adult↗

A reduction in multiple pregnancies following the use of a clomiphene citrate: human gonadotrophin sequence.

The results of stimulation with gonadotrophins at the Sterility Clinic (Crown Street) are presented. Two different techniques have been employed involving 86 patients. All patients have similar indications for treatment. All have received the same preliminary investigations and all have been treated previously with a minimum of three cycles of Clomiphene Citrate without satisfactory response (i.e. "clomid failures). Technique (1) involved 51 patients and consisted of daily injections of Human Pituitary Gonadotrophin (H.P.G.) followed by an ovulating injection of Human Chorionic Gonadotrophin (H.C.G.) and a follow up injection of H.C.G. on post-ovulatory Day 7 or 8. This technique had a pregnancy rate of 64 per cent and a multiple pregnancy rate of 34 per cent. Technique (2) involved 35 patients and consisted of 5 days priming with Ethinyl Oestradiol and Clomiphene Citrate together, followed immediately by daily injections of H.P.G., then an ovulating injection of H.C.G. and a follow up injection of H.C.G. on post-ovulatory Day 7 or 8. The results of this variation in technique were a pregnancy rate of 69 percent, a multiple pregnancy rate of 8 percent. It is suggested that the use of Clomiphene Citrate in the latter technique acts as a "buffer" against the more extreme ovarian responses to H.P.G. acting alone and has the apparent advantage of a higher pregnancy rate, a lower multiple pregnancy rate and a reduction in the number of foetuses in each of the multiple pregnancies.

Chorionic Gonadotropin↗

Coffee and alcohol intake, smoking and risk of multiple pregnancy.

We analysed the relationship between coffee and alcohol intake, smoking and risk of multiple pregnancies using data from a case-control study on risk factors for multiple births conducted in Italy. Cases were 133 women who delivered multiple births not related to treatment for infertility (33 monozygotic and 100 dizygotic twins). Controls were 395 women admitted for normal delivery at the same clinic where cases had been identified. The odds ratios (OR) of multiple pregnancy were 1.5[95% confidence interval (CI) 0.8-2.8] and 2.0 (95% CI 1.0-3.7) for women drinking respectively one to two or three or more cups of coffee per day in comparison with non-coffee drinkers. Considering separately dizygotic and monozygotic pregnancies, the estimated OR were respectively for women drinking three or more cups of coffee, 1.7 and 3.1 for dizygotic and monozygotic pregnancies. The risk of multiple pregnancy tended to be higher in women drinking >or= 15 alcohol drinks per week: in comparison with tea-totallers the estimated OR for drink > or = 15 glasses per week were 2.3 and 2.6 respectively for dizygotic and monozygotic pregnancies. Heavy smokers (> or = 10 cigarettes per day) were at increased risk of multiple pregnancy: in comparison with never smokers, the estimated OR for multiple pregnancy was 1.6 (95% CI 0.9-2.7). Considering separately the two groups of multiple pregnancy, the OR of dizygotic and monozygotic pregnancy were 1.4 (95% CI 0.8-2.5) and 2.4 (95% CI 0.9-6.1) for women smoking > or = 10 cigarettes/day, but the trend in risk with number of cigarettes smoked per day and duration of the habit was not significant.

Adult↗

Embryo quality is more important for younger women whereas age is more important for older women with regard to in vitro fertilization outcome and multiple pregnancy.

OBJECTIVE: To determine the efficiency of embryo scoring systems for multiple pregnancy in women undergoing IVF procedures. DESIGN: Retrospective record analysis. SETTING: University hospital, tertiary medical center. PATIENT(S): Three hundred one patients undergoing controlled ovarian stimulation, IVF/intracytoplasmic sperm injection (ICSI), and day 3 embryo transfer. INTERVENTION(S): IVF/ICSI and embryo transfer. MAIN OUTCOME MEASURE(S): Rate of pregnancy and rate of multiple pregnancy. RESULT(S): The score of the best three embryos (Top3) was more correlated with IVF outcome than were the number of good embryos (P=.009) or the cumulative embryo score (P=.038). In the logistic regression model, Top3 was more relevant to IVF outcome and multiple pregnancy for younger patients than was age (P<.05). For older patients, age was more correlated with IVF outcome and multiple pregnancy than was embryo morphology (P<.05). CONCLUSION(S): The embryo morphology criteria can help reduce the number of embryos transferred into younger patients. We could use the age of patients as an indicator to determine the number of embryos transferred into older patients.

Adult↗

Maternal physiology and complications of multiple pregnancy.

Approximately 1% to 3% of all pregnancies in the United States are multiple gestations. The vast majority (97-98%) are twin pregnancies. Multiple pregnancies constitute significant risk to both mother and fetuses. Antepartum complications-including preterm labor, preterm premature rupture of the membranes, intrauterine growth restriction, intrauterine fetal demise, gestational diabetes, and preeclampsia-develop in over 80% of multiple pregnancies as compared with approximately 25% of singleton gestations. This article reviews in detail the maternal physiologic adaptations required to support a multiple pregnancy and the maternal complications that develop when these systems fail or are overwhelmed.

Female↗

Controversial issues in the management of multiple pregnancies.

The management of multiple pregnancies represents a true challenge for all sub-specialties concerned with perinatal medicine. Many issues were neglected over the years merely because they were rare and therefore considered not sufficiently important to merit clinical trials. This paper discusses a personal selection of controversial issues, such as multifetal pregnancy reduction of triplets and twins, special cases in multifetal pregnancy reduction, need for invasive genetic studies, management of twin-twin transfusion, discordant fetal conditions, the definition of "term" in multiples, and the controversy about the mode of delivery.

Delivery, Obstetric↗

[Multiple pregnancy--a significant complication of in vitro fertilization protocols].

OBJECTIVE: To evaluate the history of pregnancies after IVF-ET, to define multiple pregnancy risk factors. DESIGN: A retrospective analysis of the period of 1992-2000. SETTING: Department of Gynecology and Obstetrics, University Hospital, Palacký University, Olomouc. METHODS: 343 pregnancies were evaluated, divided into 4 groups according to the patients' ages: < or = 29 yrs. (n = 150), 30-34 yrs. (n = 122), 35-39 yrs. (n = 66), > or = 40 yrs. (n = 5). The number of transferred embryos and frequency of pregnancies in relation to the patient' ages were compared as well as the multiple pregnancy and spontaneous abortion rates. The dependence of preterm labour rate, foetus weight and the incidence of operative delivery on the frequency of pregnancies were evaluated (n = 276). The data were analysed using the chi 2 and Sheffe tests. RESULTS: Three or four transferred embryos markedly increase the number of multiple pregnancies (P < 0.01). No relation to the patient's ages was found. An increased incidence of operative deliveries (P < 0.01) as well as preterm deliveries (P < 0.05) in multiple pregnancies was found. CONCLUSIONS: The number of transferred embryos is the most important risk factor for multiple pregnancy development. It is recommended to decrease the number of transferred embryos to two or one per ET.

Abortion, Spontaneous↗

Obstetrical results after embryonic reductions performed on 34 multiple pregnancies.

Thirty-four women with multiple pregnancies (three or more fetuses) underwent embryonic reduction in order to reduce abortions, premature births or fetal growth-retardation by obtention of twins. Four early abortions occurred. Thirty pregnancies reached term and out of 60 fetuses, 58 infants were born alive. Fetal death in utero of one twin occurred in two pregnancies. The mean term until delivery was 36 +/- 2.8 weeks gestation and the prematurity rate was 51.7%. Of 55 neonates, 25 were underweight within the 10th percentile and 10 out of 55 neonates were underweight below the 3rd percentile. There were three deaths in the early neonatal period. The rate of perinatal mortality was 8.3%. Fifty-four children are currently healthy and one child has a mild axial hypotonia. A reduction in prematurity was observed with a gain of 2 weeks on reported data concerning triplet pregnancies. The rate of low-birth-weight infants was high, 63.5% being underweight at birth.

Abortion, Incomplete↗

Low multiple pregnancy rate in combined clomiphene citrate--human menopausal gonadotrophin treatment for ovulation induction or enhancement.

Sixty-five infertile women, 37 with anovulation, eight with ovulatory disturbances and 20 with unexplained infertility were treated by a combination of clomiphene citrate (CC) from cycle day 5 (or 3) and human menopausal gonadotrophin (HMG) begun 3 days later for induction or enhancement of ovulation. Monitoring was carried out by measuring preovulatory 17-beta-oestradiol (E2) and progesterone (P) concentrations in blood samples and by follicle measurements using ultrasound. Forty-seven pregnancies resulted with a multiple pregnancy rate of 7.7% for those completed. This incidence is very low and within the range found for CC induction and might result from the later commencement of stimulation compared with many other protocols. These results were achieved with a low incidence of ovarian hyperstimulation syndrome (2.6% per cycle). The HMG doses given were low in comparison with those found in other forms of induction. The deleterious effects of this combined mode of induction on cervical mucus and the occurrence of premature spontaneous ovulation were much less than in the sequential mode of treatment. These results suggest that combined induction treatment by CC and HMG as described offers a means of achieving low rates of multiple pregnancies a known complication in the induction of ovulation.

Adult↗