Incidence Of Multiple Pregnancies Research Articles

Single embryo transfer and IVF/ICSI outcome: a balanced appraisal

This review considers the value of single embryo transfer (SET) to prevent multiple pregnancies (MP) after IVF/ICSI. The incidence of MP (twins and higher order pregnancies) after IVF/ICSI is much higher (approximately 30%) than after natural conception (approximately 1%). Approximately half of all the neonates are multiples. The obstetric, neonatal and long-term consequences for the health of these children are enormous and costs incurred extremely high. Judicious SET is the only method to decrease this epidemic of iatrogenic multiple gestations. Clinical trials have shown that programmes with >50% of SET maintain high overall ongoing pregnancy rates ( approximately 30% per started cycle) while reducing the MP rate to <10%. Experience with SET remains largely European although the need to reduce MP is accepted worldwide. An important issue is how to select patients suitable for SET and embryos with a high putative implantation potential. The typical patient suitable for SET is young (aged <36 years) and in her first or second IVF/ICSI trial. Embryo selection is performed using one or a combination of embryo characteristics. Available evidence suggests that, for the overall population, day 3 and day 5 selection yield similar results but better than zygote selection results. Prospective studies correlating embryo characteristics with documented implantation potential, utilizing databases of individual embryos, are needed. The application of SET should be supported by other measures: reimbursement of IVF/ICSI (earned back by reducing costs), optimized cryopreservation to augment cumulative pregnancy rates per oocyte harvest and a standardized format for reporting results. To make SET the standard of care in the appropriate target group, there is a need for more clinical studies, for intensive counselling of patients, and for an increased sense of responsibility in patients, health care providers and health insurers.

The application and impact of cryopreservation of early cleavage stage embryos in assisted reproduction

The contribution of cryopreserved embryos to the overall outcomes achieved by a clinical assisted reproduction programme has increased in importance with the trend towards reducing the numbers of fresh embryos transferred following in vitro fertilisation. Although cryopreservation appears to fully preserve developmental potential in early cleavage stage embryos that survive intact, it results in a reduction in potential when blastomere loss occurs during freezing and thawing. Overall, it can be estimated that cryopreservation results in approximately a 30% reduction in the potential for pregnancy in a population of embryos. Both blastomere survival and post-thaw resumption of mitosis can act as markers of implantation potential in frozen/thawed embryos. Application of strict criteria for freezing embryos and transferring thawed embryos may enhance apparent success rates, but may also result in some pregnancy potential being discarded. The role of embryo cryopreservation in minimising the incidence of multiple pregnancy must be balanced with the need for efficiency in the quest to establish pregnancy.

Single or multiple embryo transfer following in vitro fertilisation for improved neonatal outcome: a systematic review of the literature.

The aim of the current review was to determine if single versus two or more embryos, or double versus three or more embryos, transferred to the woman of a subfertile couple at in vitro fertilisation (IVF) maximises the likelihood of pregnancy, while minimising the likelihood of multiple pregnancy and adverse sequelae. Studies were identified that reported maternal, infant and cost outcomes following embryo transfer at IVF. Three randomised trials and 17 cohort studies were included. From two randomised trials, single embryo transfer was found to result in decreased incidence of clinical pregnancy, multiple pregnancy and low birthweight. In the cohort studies for single embryo transfer compared with transfer of two or more embryos the incidence of live birth and singleton pregnancies was unchanged, and the incidence of multiple pregnancies and low birthweight was reduced. For double embryo transfer compared with the transfer of three or more embryos, the incidence of clinical pregnancy, live birth, preterm birth and low birthweight babies was reduced. Information on neonatal and maternal outcomes following transfer of different numbers of embryos is limited. Transfer of one embryo does not alter the likelihood of a singleton pregnancy or birth when compared to transfer of two or more embryos. Transfer of one or two embryos decreases the risk of a multiple pregnancy, preterm birth and low birthweight. Further large, well-designed randomised trials are required to provide maternal and neonatal outcomes of relevance to a couple undergoing IVF.

Single embryo transfer in clinical practice

The high incidence of multiple pregnancies is the main reason for adverse treatment outcome in assisted reproduction. A good strategy to avoid multiple pregnancies is elective single embryo transfer and cryopreservation of spare embryos. Important factors in an elective single embryo transfer programme are good counselling of the patients and the selection of embryos with high implantation potential. In the infertility clinic at Helsinki University Central Hospital the elective single embryo transfer programme was started in 1997 and in 2000 the transfer policy turned to single embryo transfer as primary option. In 2003 60% of fresh transfers were elective single embryo transfers and 66% of frozen transfers were single embryo transfers. It has been shown that an elective single embryo transfer programme can be adopted in daily practice and that it decreases the multiple pregnancy rate, in our programme to around 7% with acceptable overall pregnancy and delivery rates. In Finland the increased use of single embryo transfer has reduced the proportion of multiple births. Finally, a good cryopreservation programme is essential to achieve a good cumulative delivery rate without multiple pregnancies.

6. Ethical issues related to multiple pregnancies in medically assisted procreation.

In this sixth statement of the ESHRE Task Force on Ethics and Law, the focus is on the ethical issues raised by multiple pregnancies resulting iatrogenically from the use of medically assisted procreation. The incidence of multiple pregnancies and the consequences for the child are discussed, together with general and specific ethical issues. Four recommendations are made-single embryo transfer, public funding for assisted reproduction, multiple pregnancies reported as complications not successes, and a uniform method of presenting results.

Prevention of multiple pregnancies by restricting the number of transferred embryos: randomized control study

The high incidence of multiple pregnancies is a major concern in the treatment of infertility by in vitro fertilization (IVF). Risks and costs are associated with multiple pregnancies and it is important to find a way to decrease multiple pregnancies. The standard protocol for IVF includes the transfer of two or three embryos. In this study, we compared the rate of single and multiple pregnancies between patients who received two and three embryos. One hundred and sixty-nine patients were randomly divided into two groups, with 106 cycles of IVF each. Group 1 received two embryos, and group 2 three. Group 1 had total 40 (37.8%) pregnancies, while group 2 had 29 (27.4%). The number of ongoing pregnancies was 33 (31.1%) in group 1 and 26 (24.5%) in group 2. The number of baby-take-home was 32 (30.1%) in group 1 and 26 (24.5%) in group 2. These results show that there was no significant difference between the two groups in both the total and ongoing pregnancies. On the other hand, the number of twin pregnancies was 6 (15.0%) in group 1 and 12 (41.4%) in group 2, showing a significant difference. Group 1 had no triplet pregnancies, while Group 2 had two. We conclude that the transfer of two embryos reduces the incidence of multiple pregnancies while maintaining an acceptable rate of pregnancy in IVF.

Impact of transabdominal ultrasound guidance on performance and outcome of transcervical uterine embryo transfer.

To determine the impact of transabdominal ultrasound guidance on embryo transfer during IVF therapy. Retrospective analysis of 823 consecutive embryo transfers. Three hundred and sixty-seven procedures performed with transabdominal ultrasound guidance were compared to 456 cases performed with the "clinical touch" method. Ultrasound-guided embryo transfer yielded higher, but not statistically significant, clinical pregnancy (48% vs. 44%) and implantation rates (22% vs. 20%). The incidence of multiple pregnancies, ectopic and multiple pregnancy rates were similar. The frequency of negative factors typically associated with difficult transfers, such as requirement of use of tenaculum, and presence of blood or mucus in the catheter tip, were significantly lower in the ultrasound-guided group in comparison with the clinical touch group. Ultrasound-guided embryo transfer was associated with a significantly increased easiness of transfer performance; 95% of the transfers were rated as very easy in the ultrasound-guidance group compared to 87% in the clinical touch group. The use of a soft pass catheter was the only variable independently and significantly associated with pregnancy success (odds ratio = 2.74). Ultrasound-guidance facilitates embryo transfer and in combination with the use of a soft catheter should be implemented to optimize embryo transfer results.

Multiple pregnancy — The evidence for single-embryo transfer

With the introduction of numerous new technologies, human reproduction has undergone considerable development during the last 25 years. The possibilities for treating both female and male infertility are today less of a medico-technical and more of a socio-economic problem. The high incidence of multiple pregnancy is the problem that causes most concern, with impact upon the infertile couple, offspring and society. Attempts to solve this problem have been made but more work is needed.

Multiple pregnancy

The incidence of multiple pregnancies has increased considerably over the past 20 years in the western world. The number of twin pregnancies has increased by approximately 25% and the rate of triplet and higher order multiple pregnancies has more than doubled. This is due to the use of ovarian hyperstimulation and assisted reproduction techniques, and to the increasing maternal age. Multiple pregnancy can be considered as the most important adverse outcome of infertility treatment. The main determinant for outcome and management of multiple pregnancies is the chorionicity. This can be determined by ultrasound until 14 weeks of gestation. Twenty percent of all twin pregnancies are monochorionic, and 15% of these develop severe twin to twin transfusion syndrome, which is best treated by LASER separation of the communicating blood vessels. Obstetric complications associated with multiple gestation also occur more frequently in monochorionic twins. They include increased incidence of preterm labor, intrauterine growth restriction and assisted or surgical delivery. Neonatal problems include low birthweight and increased prevalence of congenital malformations. Overall, there has been a decrease in neonatal mortality of twins and triplets over the past 10 years, which is mainly due to the enormous advances in neonatal intensive care.

A Prospective Comparative Study on IVF Outcomes with Either Purified FSH or Human Menopausal Gonadotrophin in Downregulated Normogonadotrophic Women

Objective: In compare the use of purified follicle-stimulating hormone with that of a preparation containing follicle-stimulating hormone and luteinizing hormone in infertile females undergoing IVF. Design: Open-labelled prospective controlled single-center study. Setting: Nile Badrawy IVF unit. Participants: 153 infertile females undergoing their first cycle of IVF divided into 2 groups. Interventions: Ovarian stimulation was done with either highly purified FSH for group 1 (n = 75) or human menopausal gonadotrophin group 2 (n = 78) after pituitary desensitization commenced in the midluteal phase of the preceding cycle. Monitoring was performed by ultrasound transvaginal oocyte retrieval followed by IVF and transfer of three embryos. Outcomes: Number of oocytes >18 mm at day of hCG, fertilization rate, embryo transfer rate, clinical pregnancy rate and incidence of ovarian hyperstimulation syndrome. Results: The response to ovarian hyperstimulation was similar in both groups. The number of follicles >18 mm achieved at day of hCG was 12.3 ± 0.9 (mean ± SEM) following stimulation with 38.3 ± 0.9 ampoules of Fostimon The Menogon-treated group needed 39.1 ± 0.8 ampoules to produce 11.6 ± 0.7 follicles. Fertilization rate (2PN/cell) was 58.6 vs. 64.2% in the Fostimon and Menogon group, respectively (p > 0.05). The number of embryos transferred per woman was 3.1 ± 0.1 in the Fostimon group and 3.6 ± 0.1 in the Menogon group. The pregnancy rate per woman was 33.3 vs. 25.6% in the Fostimon- and Menogon-treated groups, respectively (p > 0.05). Miscarriage rate was 16 vs 20%, respectively. However, the incidence of multiple pregnancies was significantly higher in the Fostimon-treated group (32%) vs. 10% only in the Menogon-treated group (p < 0.01). Conclusion: Purified FSH yields similar clinical outcome to hMG in terms of oocytes retrieved and clinical pregnancies in a standard IVF regimen.

Neonatal and long-term outcomes of very low birth weight infants from single and multiple pregnancies

The revolution in artificial reproductive technologies has resulted in a dramatic rise in the incidence of multiple pregnancies. Many of these infants are born prematurely, often extremely so. Consequently, perinatal morbidity and mortality are highly correlated with plurality. The primary mechanism for this increased risk is prematurity. Studies of the relationship between plurality and outcome are frequently hampered by major differences in case mix between singletons, twins and high multiples. For example, high multiples tend to receive earlier prenatal care, receive more antenatal steroids, are more often delivered by Caesarean section and more often suffer from respiratory distress syndrome. However, recent studies that appropriately account for relevant confounding variables have suggested that very low birth weight infants from high multiple pregnancies are at excess risk for mortality when compared with twins and singletons. This article reviews the current available evidence.

The effects on offspring of premature parturition.

The time of parturition defines the length of the intrauterine period of fetal life, a requisite to achieve adequate adaptation to the external environment. Immaturity, a condition whose severity is inversely related to the length of pregnancy, is the main determinant of the increased morbidity and mortality associated with preterm birth. Despite great advances in medical technology and expertise, mainly after the introduction of the neonatal intensive care units, only one- to two-thirds of infants from the subsets with lower birthweight/gestational age reach survival at discharge. Distinct major neurological and sensorial sequelae, including cerebral palsy, retinopathy of prematurity, and hearing loss, as well as reduced neuropsychological abilities, leading to deficient academic achievement and deterioration of several aspects of health status, are still highly prevalent among the most immature children. Interestingly, decreasing mortality rates, which are not followed by detectable increases of disability, are being observed in recent years. Future advances may be expected from clinical and basic research on uterine contractility and cervical softening. Also, changes in reproductive technology procedures, a main factor in the incidence of multiple pregnancies, and a more refined approach to obstetric care, compose some of the clinical interventions which may reduce the problem.

Clinical outcomes with transfer of blastocyst or cleavage stage embryos: high order pregnancies, newborn weights and sex ratios.

Objective: We have previously reported our preliminary clinical experience with the culture and transfer of blastocyst stage embryos. Here, we report results of a retrospective analysis compiling our clinical outcome experience for now two years (1999–2000 period). Design: Retrospective analysis. Materials/Methods: In a total of 599 consecutive unselected cycles in which couples were given the opportunity to have extended culture, implantation rates (gestational sacs/embryos transferred) were 16.5% (182/1100) after day 3 embryo transfers (D3 ET) and 27.2% (157/578) after blastocyst transfers (D5,6 ET), (P < 0.0001). The mean number of embryos transferred was 3.2 ± 0.9 vs. 2.3 ± 0.6 for D3 ET and D5,6 ET, respectively (P < 0.0001). Results: Outcome measures for both groups are shown in the table below. The overall incidence of multiple pregnancy (defined as two or more gestational sacs) is not decreased with D5,6 ET; however, a significant reduction in the frequency of triplet pregnancies is observed with D5,6 ET (P < 0.01). At the time of writing 182 babies have been born. The sex ratio (males:females) in babies from D3 ET (49:51, n = 100) was not different from that of babies from D5,6 ET (47:35, n = 82), (P = 0.3). Likewise, no differences in birth weights were noted for male or female babies born after the transfer of blastocysts vs. cleavage stage embryos (male babies: 2568.5 ± 884.5 grams vs. 2574.2 ± 779.6 grams for D5,6 ET and D3 ET, respectively, P = 0.9; female babies: 2789.6 ± 720.0 grams vs. 2565.7 ± 873.2 grams for D5,6 ET and D3 ET, respectively, P = 0.2). Clinical outcomes after transfer of Day 3 embryos or Blastocyst stage embryos. Tabled 1ParameterDay 3 ET (No. and %)Blastocyst ET (No. and %)P value (Fisher’s exact test)Chemical pregnancies(Positive HCG’s)149/343 (43.4)123/256 (48.0)n.s.Clinical pregnancies (gestational sacs)118/343 (34.4)108/256 (42.2)0.06Singletons68/118 (57.6)63/108 (58.3)n.s.Overall frequency of multiples50/118 (42.4)45/108 (41.7)n.s.Twins37/118 (31.3)42/108 (38.8)n.s.Triplets12/118 (10.2)2/108 (1.9)0.01Quadruplets1/118 (0.8)1/108 (0.9)n.s.Monozygotic twins3/118 (2.5)1/108 (0.9)n.s. Open table in a new tab Conclusions: The high rate of twins with D5,6 ET (38.8%) warrants evaluation of single blastocyst transfers.

Multiple pregnancies and assisted reproductive technologies.

We are in the midst of an historically unprecedented increase in the incidence of multiple pregnancy. Throughout the 20th century, infant mortality has declined more than 90%, to 7.2/1000 live births. However, in the latter part of the 20th century, the decline in neonatal mortality is more attributable to improved rates of survival of low birth weight infants than to the reduction in incidence of low birth weight. Low birth weight is associated with longterm effects, such as neurological disorders, learning disabilities, and delayed development. Multiple births are 8 times more likely to be low birth weight than are singleton births. Half of all twins and 90% of all triplets and higher multiple births are low birth weight. Two possible sources of the observed increase in multiple births are increasing use of ovulation induction and increasing use of assisted reproductive technology (ART) procedures to treat infertility. In 1990, the Centers for Disease Control and Prevention (CDC) estimated that liveborn infants delivered as a result of ART procedures represented only 17.3% of quadruplet and 11.4% of quintuplet infants born in the United States. The costs of caring for the premature and low birth weight infant can range from $20,000 to $400,000 per baby, compared with less than $7000 for an uncomplicated birth. It is time to recognize that the cost of management of multiple pregnancy is an integral part of the cost of infertility treatment. Investigation into factors that could decrease the risk of generating multiple pregnancies while still optimizing the possibility of achieving pregnancy is essential. We should discourage insurance policies that favor such procedures as controlled ovarian hyperstimulation/intrauterine insemination (COH/IUI) over other ART interventions that are less likely to result in multiple pregnancies.

Anaesthesia for assisted conception

Anaesthesia for assisted conception

The influence of sperm morphology and the number of motile sperm inseminated on the outcome of intrauterine insemination combined with mild ovarian stimulation

To determine the influence of sperm morphology and the number of motile sperm inseminated on the outcome of IUI in hMG-stimulated cycles and to establish lower limits for these variables below which the expectation of pregnancy is limited. Retrospective study of data from 1990 to 1992. Tertiary referral Reproductive Medicine Unit. Couples with bilaterally patent fallopian tubes, and > or = 200,000 motile sperm recovered in a trial preparation before treatment. No other semen criteria were used to exclude couples. Women were stimulated with hMG irrespective of whether they were ovulatory or anovulatory. The study comprised 163 couples who underwent 330 cycles. Pregnancy rate (PR) per cycle was related to the percentage normal sperm morphology in the fresh semen sample and the number of motile sperm inseminated after sperm preparation by swim-up or Percoll gradients. The overall PR was 16.1% per cycle. The PR was highest in the first cycle of treatment (21.4%) and declined in the second and third cycles. The miscarriage rate was 10.4% and the incidence of multiple pregnancies was 13.9%. Two groups of patients were defined on the basis of sperm morphology: a "poor outcome" group ( < or = 10% normal) and a "good outcome" group ( > 10% normal). The PRs in these two groups were 4.3% and 18.2%, respectively, and the cumulative PRs after three cycles were 8.3% and 40.1%, respectively. The number of motile sperm inseminated did not significantly affect the PR. The degree of teratozoospermia affected the PR in hMG-stimulated IUI cycles and a normal morphology value of 10% in the fresh semen distinguished couples with good and poor outcomes. In contrast, the number of motile sperm inseminated did not significantly influence IUI outcome.

The outcome of multiple pregnancy.

The incidence of multiple pregnancy and delivery has increased dramatically over the past 10-15 years in many developed countries of the world. Data for England and Wales show that between 1980 and 1993 the twin maternity rate increased by approximately 25% and the triplet and higher order maternity rate more than doubled. Similar trends have been reported elsewhere. The majority of these increases have been linked to the use of ovarian stimulants and assisted reproduction techniques, and multiple pregnancy must be considered to be one of the most important adverse outcomes in current methods of infertility treatment. Obstetric complications associated with multiple pregnancy include prenatal screening problems and increased incidence of pregnancy-induced hypertension, antepartum haemorrhage, preterm labour and assisted or surgical delivery. Neonatal problems include low birthweight and increased prevalence of congenital malformations. Compared with singletons, neonatal mortality was seven times higher in twins and > 20 times higher in triplets and higher order births in England and Wales in 1991. Survivors also suffer higher rates of cerebral palsy and other neurological impairments. Most studies of pregnancies and babies resulting from assisted reproduction have demonstrated similar, if not higher, risks of adverse obstetric and neonatal outcomes for multiple births compared with national expectations. A poorer outcome in multiple pregnancy, especially in triplet and higher order pregnancy, supports the replacement of two good quality embryos in assisted reproduction treatment cycles.

Pregnancy: First trimester embryo reduction: a medical solution to an iatrogenic problem

The incidence of multiple pregnancies is increasing, mainly as a consequence of the widespread use of various infertility protocols. Since such gestations present a high risk of feto-maternal morbidity and mortality, selective first trimester fetocide remains one of the few reasonable options. We reviewed the literature dealing with the outcome of 804 multiple pregnancies following the use of transcervical, transvaginal or transabdominal approaches. Questions relating to dealing with technical failure, method of fetocide and procedural improvements are examined. In a comparison of the variables: miscarriage, preterm delivery, perinatal and neonatal loss rates, the transvaginal approach fares better, but statistical significance (P < 0.001) is achieved only for preterm delivery. We speculated that this might be attributable to the very early gestational age at which the procedure is usually performed. However, the transabdominal approach offers better results when post-manipulation maternal morbidity is considered, i.e. infection and vaginal bleeding. Since each option offers different advantages and disadvantages, additional experience and larger population samples are required to further clarify this important issue.

Idiopathische Subfertilität: Schwangerschaftsraten nach IVF-Behandlung im minimal stimulierten monofollikulären Ovarialzyklus

Fifty-nine patients with idiopathic subfertility were treated with IVF in 176 minimally stimulated cycles. Twenty pregnancies were achieved, resulting in pregnancy rates of 11.4% per treatment cycle and 21.3% per embryo transfer. Thus, the mode of treatment described here appears to be an useful alternative to IVF or laparoscopic GIFT in gonadotropin-stimulated cycles, since it carries good chances of success while avoiding the risk of massive ovarian hyperstimulation and increased incidence of multiple pregnancies.

Treatment of anovulation with pulsatile gonadotropin-releasing hormone: prognostic factors and clinical results in 600 cycles.

Pulsatile GnRH (pGnRH) was administered to 292 anovulatory patients in 600 consecutive cycles between February 1984 and February 1993. This represents the largest single pGnRH series ever reported. Patients were divided into the following groups: primary hypogonadotropic amenorrhea (PHA), 73 patients, 161 cycles; other hypogonadotropic hypogonadisms (OHH), 57 patients 107 cycles; multifollicular ovary (MFO), 39 patients 75 cycles; polycystic ovary (PCO), 85 patients 172 cycles; and other hyperandrogenic anovulations (OHA), 38 patients 85 cycles. GnRH was administered iv at a dose of 1.25-20.0 micrograms every 30-120 min; most cycles (505) were performed with a regimen of 2.5-5.0 micrograms GnRH every 60-90 min. In 228 cycles of MFO, PCO, and OHA patients, pGnRH was preceded by GnRH agonist (GnRH-A) suppression. Ovulatory rates were 75%, and pregnancy occurred in 105 cycles (pregnancy rate of 18%/treatment cycle and 23%/ovulatory cycle). Ovulatory and pregnancy rates were higher in PHA, OHH, and MFO and lower in PCO and OHA. Only 4 multiple pregnancies occurred (3.8%), none after GnRH-A suppression. The abortion rate was 30% and was highest in PCO (45%). GnRH-A pretreatment improved ovulatory rates only in PCO (from 49% to 71%; P < 0.001), whereas it had no significant effect on pregnancy and abortion rates in any group. Higher weight and insulin were associated with lower ovulatory and pregnancy rates; higher LH and testosterone were associated with lower ovulatory rates only. We conclude that 1) pGnRH is a highly effective ovulation induction method; 2) pGnRH does not cause ovarian hyperstimulation; 3) low dose pGnRH is associated with a remarkably low incidence of multiple pregnancy; 4) GnRH-A pretreatment improves pGnRH outcome in PCO and further lowers the incidence of multiple pregnancy; 5) pGnRH is associated with relatively elevated abortion rates, particularly in PCO; and 6) pGnRH is less successful in overweight patients and when high baseline LH, testosterone, and insulin levels are present.