Treatment of anovulatory infertility: the problem of multiple pregnancy

The aim of the study was to assess patient, treatment and cyclecharacteristics in relation to the risk of multiple conceptionfollowing ovulation induction in order to reduce the prevalenceof this complication of treatment. We performed a retrospectiveanalysis of 208 pregnancy cycles achieved in the Middlesex Hospitaloutpatient fertility unit. These pregnancies were achieved in175 anovulatory women who conceived after gonadotrophin or pulsatileGnRH therapy. The multiple conception rate was 13.4%. Afterspontaneous reductions and abortions the multiple delivery ratewas 9.6%. Clinical features associated with an increased riskof multiple pregnancies were the presence of polycystic ovarysyndrome and secondary infertility. Comparison between differentprotocols of ovulation induction revealed no relationship withthe risk of multiple conceptions. Although total number of follicleswas increased in the multiple conception cycles, the distributionof follicles according to their diameter on the day of humanchorionic gonadotrophin (HCG) administration was similar inmultiple and singleton conception cycles. Thus, the risk ofmultiple conception could not be attributed to an increasednumber of follicles of any particular size but directly relatedto the total number of the cohort follicles (5=14 mm) and leadingfollicles (>17 mm), rising from 7% with one follicle to 33%with six or more follicles. As we could not find a specificpattern of follicular development that could be associated withmultiple conception, we conclude that the difference in theovarian response leading to multiple conception is quantitativerather than qualitative. The data presented enable the assessmentof the risk of multiple conception in any given cycle.     

The management of multiple pregnancies after induction for superovulation

The high rate of multiple pregnancies after embryo transferdepends upon the number of embryos replaced and amounts to {smalltilde}20% for four or more embryos. This incidence justifiesa preventive or curative treatment after the induction of superovulation.Aspiration of one or more embryos via the cervix under ultrasoundcontrol has been undertaken on 42 patients since 1983, and involvedtwo sextuplets, 10 quadruplets, 18 triplets and 12 twins. Twentysix embryo reductions were performed before 9 weeks of amenorrhoea.Five failures after 9 weeks were due, in the early stages ofthis procedure, to infection. In the case of twins, the indicationwas a scarred uterus in 10 cases and a psychiatric reason fortwo patients. In 19% of our cases delivery occurred within 32weeks of amenorrhoea.     

Embryo reduction in multifetal pregnancies using saline injection: comparison between the transvaginal and the transabdominal approach.

A total of 30 patients with multifetal pregnancies, all resulting from treatment with superovulatory agents or assisted reproductive techniques, underwent embryo reduction. All patients had three or more fetuses (one sextuplet, two quintuplets, seven quadruplets and 20 triplets). The procedure was carried out using intra-embryonal injection of 0.9% sodium chloride solution. Embryo reduction was carried out via the transabdominal approach in 10 patients, performed at 11-12 weeks of gestation, and via the transvaginal route in 20 other patients, at 8-10 weeks of gestation. In the transabdominal group, one patient aborted following repeated attempts at embryo reduction while the other nine gave birth to healthy newborns (eight twins and one triplet). In the transvaginal group, four pregnancies are currently ongoing (all beyond 28 weeks of gestation), 14 pregnancies resulted in a delivery of at least one live newborn (13 twins and one singleton), one patient had a late abortion at 24 weeks' gestation and another was delivered at 27 weeks' gestation due to severe pre-eclampsia. Transvaginal ultrasound-guided needle procedures are commonly practised in most in-vitro fertilization units. The employment of this route for embryo reduction, performed at an earlier gestational age and with the use of a non-toxic substance such as 0.9% saline solution, is advocated.     

Risk factors for high-order multiple implantation after ovarian stimulation with gonadotrophins: evidence from a large series of 1878 consecutive pregnancies in a single centre

BACKGROUND: High-order multiple pregnancies (triplets or more) have a large adverse impact on perinatal morbidity and mortality as well as important economic consequences. Most triplets and higher births are due to ovulation induction alone or in combination with intrauterine insemination (IUI) rather than to in-vitro fertilization (IVF). The present investigation was undertaken to determine whether there were specific variables that related to patient clinical characteristics (age of the woman, duration of infertility, type of infertility, body mass index, basal FSH and LH concentrations), treatment characteristics (initial dose of gonadotrophins, total dose of gonadotrophins administered, number of days of ovarian stimulation, insemination procedure, number of spermatozoa inseminated in patients undergoing IUI, type of luteal support), and ovarian response (oestradiol serum concentrations, number and size of follicles) that might be associated with the occurrence of high-order multiple implantation in order to develop a prediction model. METHODS: This study employed univariate, multivariate and receiver-operating characteristic (ROC) analysis of a large series of 1878 consecutive pregnancies obtained in cycles stimulated with gonadotrophins. Of them, 1771 (94.3%) were low-order pregnancies (1477 singletons and 294 pairs of twins) and 107 (5.7%) were high-order pregnancies. RESULTS: Predictive variables in the multivariate analysis were age of the woman, serum oestradiol concentrations and number of follicles >10 mm on the day of HCG injection. Stratification of the number of follicles into three categories (1 to 3, 4 to 5, and >5 follicles respectively), peak serum oestradiol and woman's age according to the ROC curves, showed that the risk of high-order multiple implantation correlated significantly with increasing total number of follicles and was significantly increased in women with a serum oestradiol >862 pg/ml and aged < or =32 years. CONCLUSIONS: This three-variable model can help to identify patients at high-risk for high-order multiple pregnancy in ovulation induction cycles.     

Follicular diameters in conception cycles with and without multiple pregnancy after stimulated ovulation induction

BACKGROUND: Controlled ovulation induction and intrauterine insemination (OI-IUI) is associated with multiple pregnancies, which are a cause of much concern. No reliable datasets have shown clear criteria for predicting multiple pregnancy. The aim of this study was to eliminate a number of variables by examining only conception cycles to determine ultrasound criteria posing risks of multiple pregnancy. METHODS: 112 OI-IUI conception cycles (multiple pregnancy rate 19.6%) were analysed retrospectively to identify factors that may be used to evaluate multiple pregnancy risk. Analyses of ultrasound data on the day of hCG administration allowed study of the role of primary, secondary and tertiary follicle diameters (FD). RESULTS: There were no multiple pregnancies in cases where there was a single FD > or = 14 mm, and no higher-order pregnancies where the tertiary follicle measured <14 mm. Follicles with an FD of 15 mm showed an 8% attributable implantation rate. CONCLUSIONS: Revision of the criteria for administration of the ovulatory dose of hCG should include the concept that follicles of 15 mm diameter may yield a pregnancy. We suggest that rigorous application of such criteria (critical FD of 16 mm combined with secondary FD evidence) will not reduce the programme pregnancy rate, but will reduce the incidence of multiple conceptions.     

Maternal plasma concentrations of insulin-like growth factor binding protein-1 and placental protein 14 in multifetal pregnancies before and after fetal reduction

The aim of this study was to investigate the changes in maternalplasma insulin-like growth factor binding protein-1 (IGFBP-1)and placental protein 14 (PP14) in multifetal pregnancies beforeand after embryo reduction. Maternal plasma IGFBP-1 and PP14were measured serially in three groups of pregnant women at8–21 weeks gestation. Groups 1 and 2 were 12 singletonand 12 twin pregnancies achieved after in-vitro fertilization(IVF). Group 3 comprised 26 women with multifetal pregnanciesundergoing embryo reduction to twins. In the IVF pregnanciesmaternal plasma IGFBP-1 and PP14 increased with gestation toreach a peak at 20 and 10 weeks respectively; the mean concentrationsin twin pregnancies were significantly higher than in singletons.In multifetal pregnancies the mean plasma concentration of bothproteins was similar to that of IVF twin pregnancies beforereduction; after reduction, the values fell to less than thoseof twins. These findings suggest that the maximum secretorycapacity of the endometrium is achieved with twin pregnancies.In multifetal pregnancies undergoing iatrogenic reduction totwins, total residual endometrial function was less than intwin conceptions.