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Objective To determine whether the psychosocial risks associated with multiple births are increased as a consequence of the use of assisted reproductive technology (ART) in comparison with those not resulting from ART. Design Cross-sectional study. Setting Fertility units of a university hospital and a private hospital. Patient(s) Parents of single children and multiples (twins and triplets) between 6 months and 4 years of age (n = 636) were divided into two groups: those who conceived through ART (n = 265) and those who conceived through non-ART (n = 371). Intervention(s) Administration of six scales, in office or by mail. Main Outcome Measure(s) Measurement scales of material necessities, social stigma, marital satisfaction, perceived stress, depression, quality of life, and their subscales. Result(s) The analysis of variance, Student's t -test, and χ 2 -test were applied. No effect was observed based on the use of ART in the psychosocial variables studied. Significant differences were obtained between the groups of single (SB) and multiple births (MB) with respect to material necessities, social stigma, marital satisfaction, depression, and quality of life. Conclusion(s) Having more than one child per birth, whether resulting from the use of ART or not, increases psychosocial risks for the parents. Assisted reproduction centers should include this information with the obstetric and neonatal risks, stressing the advantages of having one child per birth. Psychosocial risks are not increased as a result of having used ART, but the goal of avoiding the repeated use of ART does influence the desire to transfer the maximum number of embryos possible. Psychological counseling should be included before initiating ART, as well as when a multiple pregnancy is confirmed.

Objective To compare the impact of mandated IVF insurance coverage on ET practices and resulting multiple pregnancy rates. Design Retrospective analysis of all fresh, nondonor IVF cycles performed in the United States in 2006. Setting United States. Patient(s) A total of 91,753 fresh, nondonor IVF cycles in the United States. Intervention(s) None. Main Outcome Measure(s) Pregnancy rate, live-birth rate, embryos transferred, multiple pregnancy rate. Result(s) Overall, nonmandated states had a significantly higher pregnancy rate (38.8% vs. 35%) and live-birth rate (32.2% vs. 29.1%) than mandated states. Nonmandated states also had a significantly higher twin rate (28.1% vs. 26%) and triplet rate (3.9% vs. 3.4%). The average number of embryos transferred was also significantly higher in nonmandated states (2.6 vs. 2.2). These findings were more pronounced in the Conclusion(s) In the last 8 years, despite a reduction in the average number of embryos transferred and multiple pregnancy rates, there is a continued association between mandated IVF coverage, the transfer of fewer embryos, and lower rates of multiple pregnancies and births, particularly in the younger age groups.

To determine the prevalence and the relative benefits conferred by selective and spontaneous reduction of one or more fetuses in trichorionic triamniotic triplet pregnancies on time to delivery.Retrospective cohort study.Academic medical center.IVF patients with trichorionic triamniotic triplets between January 1998 and December 2007.None.Gestational length at time of delivery.Selective reduction to twins was used in 87 of the 153 (56.9%) triplet pregnancies that did not spontaneously reduce prior to12 weeks, and was associated with longer gestation (13.9 days) with a fourfold greater likelihood of delivery at ≥ 34 weeks' gestation (odds ratio [OR], 4.3; 95% confidence interval [CI] = 2.2-8.6), compared with pregnancies not undergoing selective reduction. Compared with ongoing triplets, spontaneous reduction at12 weeks' gestation (28 cases) was associated with longer gestation (13.7 days) and significantly greater likelihood delivering at or after 34 weeks' gestation (OR, 3.7; 95% CI, 1.4-9.9).Selective reduction of one fetus was used in 56.9% of patients in this population. Early spontaneous reduction (12 weeks) and selective reduction to twins each conferred similar benefits by extending time to delivery and increasing the likelihood of delivery at or after 34 weeks' gestation.

To evaluate factors associated with the use of elective single embryo transfer (eSET) and its effect on assisted reproductive technology (ART) outcome.Historical cohort.Clinic-based data.A total of 69,028 ART cycles of autologous fresh embryo transfers with additional embryos cryopreserved during the same cycle performed during 2004-06 and reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database.None.Factors associated with the number of embryos transferred, and the odds of pregnancy, live birth, and multiple-infant live birth by number of embryos transferred as adjusted odds ratios (AORs).Single embryo transfer was used more with uterine factor (AOR 1.76) and less with male factor, endometriosis, or tubal factor (AOR 0.81, 0.72, 0.83, respectively). Compared with women aged30 years, eSET was used less among women aged 35-39 years andor =40 years (AOR 0.74 and 0.39, respectively). Compared with White women, eSET was used more with Asian (AOR 1.52) and less with Black or Hispanic women (AOR 0.73 and 0.67, respectively). Compared with eSET, the likelihood of pregnancy, live birth, or multiple-infant live birth was more likely with two embryos (AOR 1.33, 1.34, and 27.4, respectively).Elective SET, used more for younger women with specific diagnoses, is associated with slightly reduced likelihood of a live birth but much reduced likelihood of multiples.

Objective To evaluate how the ranking of IVF programs changes if high-order multiple pregnancies (HOMPs) are considered negative outcomes. Design Retrospective analysis. Setting The 2004 Society for Assisted Reproductive Technology Clinic Outcome Reporting System. Patient(s) Two hundred seven programs that performed >50 IVF cycles were analyzed, and only patients ≤35 years of age were included. Intervention(s) Program size, success rate, and number of embryos transferred were recorded for each program. All programs were ranked in accordance to these variables. Main Outcome Measure(s) The programs were re-ranked after considering HOMPs as negative, rather than as positive, outcomes. Result(s) High-order multiple pregnancies were more abundant as the number of embryos replaced increased. The live birth rate, after excluding HOMPs, significantly decreased as the number of embryos transferred increased. The lowest ranked programs performed transfers with the greatest number of embryos (2.4–4.5). After HOMP exclusion, the rank of programs that transferred >2.4 embryos decreased, as opposed to the programs that transferred fewer embryos (1.8–2.4). Conclusion(s) Reclassifying HOMPs as failed cycles will result in a reduced rank in programs that maintain high embryo replacements. Redefining success as a singleton or twin birth significantly changes the ranking order of programs and, potentially, how programs are perceived.

To investigate the consequences of a law introduced in Italy in 2004 that forbids the fertilization or injection of more than three oocytes for assisted reproduction and does not allow any embryo selection or cryopreservation.Retrospective observational analysis.Subfertile patients enrolled in an assisted reproduction program.Before the introduction of the law there were 1,179 cycles and after its enactment there were 1,860 cycles in 1,619 subfertile couples.Ovarian stimulation for IVF/intracytoplasmic sperm injection (ICSI) attempts.Pregnancy and implantation rate.Pregnancy rates (PR) per cycle (24.34% vs. 23.11%), per retrieval (28.64% vs. 25.65%), per transfer (31.37% vs. 27.74%), and the take-home babies per started cycle (19.1% vs. 18%) was not significantly different between the two periods. After introduction of the law, the PR significantly decreased in patients whose total motile sperm count was1 x 10(6) (40.85% vs. 23.62%) and in patients receiving two embryos (35.71% vs. 23.53%). This difference was mostly the result of a reduced PR in patients36 years old receiving two unselected embryos (41.16% vs. 30.90%). This result was, however, obscured by the higher proportion of patients36 years (3.9% vs. 45.12%) receiving three embryos after the enactment of the law, which lead to a significantly higher PR (28.73% vs. 37.56%) and a consequent significantly higher triplet rate (0.58% vs. 4.71%).Women in whom elective transfer of two embryos was allowed before passing the law and couples with a severe male infertility factor had significantly reduced success rates. Although the overall PR did not change after the new law, if the transfer of frozen embryos is not considered, this was mainly the result of a higher number of embryos transferred into women36 years old. This study shows how the negative effects of the new law are obscured by the transfer of a higher number of embryos in younger patients, resulting in a higher PR at the cost of a significantly higher triplet rate.

Objective To determine whether excess mortality, neonatal morbidity, and congenital malformations occurred in in vitro fertilization (IVF) conceived compared with naturally conceived singleton, twin and triplet very low birth weight (VLBW) infants. Design Population-based observational study from 1995 through 2002. Setting Israel National VLBW infant database. Patient(s) A total of 8,181 VLBW infants conceived naturally or by IVF were stratified into groups of singletons and complete sets of twins and triplets. Intervention(s) None. Main Outcome Measure(s) Neonatal mortality and morbidity. Result(s) In the unadjusted analyses, mortality and neonatal morbidity rates were generally similar between the IVF-conceived and the naturally conceived infants stratified by plurality groups. When adjusted for multiple confounding variables, no excess neonatal mortality or morbidity occurred among IVF-conceived infants. The risk for congenital malformations adjusted for ethnicity, maternal age, and parity was also not increased in the IVF-conceived groups. Conclusion(s) In our population, VLBW infants conceived by IVF were not at increased risk for congenital malformations, postnatal morbidity, or mortality when compared with naturally conceived infants.

To estimate the likelihood of adverse outcomes in triplet pregnancies by a score comprising pregravid maternal characteristics.A cross-sectional study.Triplets database collected by Matria Healthcare, Inc.A scoring system was constructed, assigning 1 point for the presence of a risk factor (nulliparity, stature165 cm, and age35 years) and 0 for the absence of a risk factor. Data related to 2,887 triplet sets were analyzed.None.Total triplet birth weight4,500 and delivery at 27-32 weeks.We identified 18% of triplets' mothers (score 3) in whom the likelihood for adverse results is 50%-90% higher and the likelihood for optimal results is 40% to 70% lower than background rates.A pregravid maternal profile could estimate the likelihood of adverse outcomes and be used for consulting patients at risk of having or carrying a triplet pregnancy.

There is evidence that parenting twins adversely affects the mother's emotional well-being, and triplet births pose even more demands. This prospective cohort study examined parenting stress and psychosocial status 1 yearpostpartum in 129 women having a single naturally conceived birth, 95 with a single in vitro fertilization (IVF) birth and 36 with a twin or (in 5 instances) triplet IVF birth. Participants entered the study at 18 weeks gestation and were followed up 6 weeks and 12 months after giving birth. Both the General Health Questionnaire (GHQ)-12 and Parenting Stress Index Short Form were administered. Multiple IVF births were associated with higher total parental stress scores than women with natural pregnancies and also more child difficulty and more dysfunctional parent-child interaction. Compared with singleton IVF births, women with multiple IVF births had significantly higher scores for total parenting stress, and also more child difficulty and dysfunctional interaction. The singleton natural and IVF birth groups did not differ significantly in these respects. Similar findings were obtained after excluding triplet births. Abnormal total parenting stress scores at and above the 85th percentile were found in 22% of the multiple IVF birth group, 5% of women with a singleton IVF birth, and 9% of those who conceived naturally. Mothers with multiple IVF births were less likely to be working outside the home at follow up. Only 26% of women with singleton IV births reported having felt depressed in the year after giving birth, compared with 41% of women who conceived naturally and 47% of those with multiple IVF births. There were, however, no significant differences in the frequency of medical treatment for depression or in GHQ scores. These findings confirm reports that having a singleton IVF birth is not associated with increased parenting stress. Parenting more than 1 young infant is demanding, especially for an inexperienced mother. The women studied were generally in stable long-term relationships and were able to pay for fertility treatment. The effects of multiple births are probably greater in socially and psychologically disadvantaged families.

If further progress is to be made in reducing the problem of multiple pregnancies, guidelines and their enforcement for the use of induction of ovulation and enhancement of ovulation are required. Collecting information on fetal reduction will also be necessary.

The data of the population-based, prospective survey of multiple births in East Flanders, Belgium, show that a greater proportion of monozygotic twins is observed with clomiphene citrate as sole treatment compared with other ovulatory drugs. Among iatrogenic monozygotic twins, the ratio of monochorionic versus dichorionic pairs is higher compared with spontaneous twins.

We conducted a retrospective, cross-sectional study to evaluate the efficacy, safety, and effect of first-trimester multifetal pregnancy reduction on procedure-related complications and obstetrical outcome in multiple pregnancies with a monochorionic component. Although procedure-related complications were relatively common, the obstetrical outcome was favorable in most cases when the monochorionic twin component was reduced.

Objective To present an unusual case of hyperreactio luteinalis and a comprehensive review of the recent literature. Hyperreactio luteinalis is a benign ovarian condition of pregnancy that at times becomes life threatening. The medical literature provides only case reports. Design Case report and systematic review of the literature. Setting University Center. Patient(s) A multiparous woman with polycystic ovary syndrome who underwent ovarian stimulation with oral and injectable medications and conceived triplets. She presented at 10 weeks of pregnancy with hyperreactio luteinalis. Intervention(s) Fetal reduction to singleton. Main Outcome Measure(s) Resolution of condition. Result(s) The condition resolved 6 weeks after fetal reduction. The patient delivered at term without further complications. Conclusion(s) Our review showed that many unnecessary surgeries are performed to treat hyperreactio luteinalis. When feasible, fetal reduction may improve outcome and represents an effective approach that does not compromise maternal well-being or future fertility.

Objective To assess the value of subzonal insemination (SUZI) in cases of total or extreme asthenozoospermia. Design The results of IVF after SUZI were assessed in six cycles (four couples) with documented asthenozoospermia. Setting Institut de Medecine de la Reproduction, Marseille, France. Patients Four couples underwent six retrieval cycles. In all cases asthenozoospermia was total (100% of immotile spermatozoa) or extreme (5% nonprogressive motility). Oligozoospermia and teratozoospermia were ruled out in all cases. In two cases electron microscopy revealed the absence of the central singlet in the flagellum axonemal complex and in one case a major dysplasia of the fibrous sheath in the flagellum principal piece. Results The overall fertilization rate was 45%. The diploid embryo rate was 33%. Embryo quality was satisfactory. In five of six cycles, three embryos were transferred. Two triplet pregnancies were obtained corresponding to an implantation rate per transferred embryo of 40%. Conclusion Total or extreme asthenozoospermia seems to be a good indication for SUZI.

Objective To evaluate the effect of selective termination in triplet pregnancies. Design Comparative, prospective, nonrandomized study. Setting All 80 pregnancies were managed in a single tertiary center by the same obstetrical team. Patients Eighty women with triplet pregnancies were divided into two groups: group I consisted of 48 women who wished to continue their pregnancies without reduction; in group II were 32 women who choose reduction generally to obtain twins. Interventions Selective terminations were performed after an average term of 9.6 weeks of gestation by transcervical or transabdominal approaches. Main Outcome Measurements The rate of miscarriage and prematurity, fetal growth, perinatal morbidity and mortality, and maternal complications in the two groups. Results Prematurity was lower in reduced pregnancies (95.5% in triplets versus 53.5%), especially between 24 to 32 weeks' gestation where prematurity was reduced by half. Birth weight was >450g higher in the reduced group. The perinatal mortality rate was lower for reduced pregnancies, but this difference was not statistically significant. Five life-threatening maternal complications occurred in triplets, with none in the reduced group. Conclusions Selective terminations are effective in decreasing the rate of prematurity, improving fetal growth, and avoiding maternal complications. The procedure thus could be used in triplet gestations. The ultimate decision should be taken by the couple who must be well informed of the risks of the procedure before deciding.

OBJECTIVE: To study the relationship between the quality of the transferred embryos and the occurrence of multiple pregnancies. Embryo quality was defined by the cleavage rate and by morphological parameters such as blastomere size and the presence or absence of anucleate fragments. DESIGN: A retrospective analysis of 1,915 consecutive transfers of fresh embryos between January 1986 and December 1989. SETTING: All the embryo transfers (ETs) were performed in patients from the in vitro fertilization program of the Center for Reproductive Medicine, Vrije Universiteit Brussel, Brussels, Belgium. RESULTS: We confirmed the relationship between the number of embryos transferred and the pregnancy rate (PR): 11.9% of the single, 19.0% of the double, and 34.1% of the triple ETs were successful. Thirty-one percent of these triple embryo replacements resulted in a multiple gestation. At the time of transfer (44 to 48 hours after insemination), we observed that embryos that had undergone at least two mitotic divisions implanted better than two-cell embryos of comparable morphological appearance (implantation rate per transferred embryo: 21.3% versus 12.3%, P less than 0.001) and that heavily fragmented embryos did not implant as well as embryos without or with fewer anucleate fragments (1.5% versus 14.1%, P less than 0.001). The PR, implantation rate, and the incidence of multiple pregnancies increased significantly with the number of good quality embryos that were transferred. CONCLUSIONS: Our study indicated that embryo quality based on morphological observations could predict the occurrence of multiple pregnancies.

Objective To report an unusual case of congenital cervical atresia and tubal factor infertility, achieving triplet pregnancy through transmyometrial embryo transfer (ET) resulting in the delivery of healthy twins after multifetal pregnancy reduction (MFPR). Design Case report and literature review. Setting University hospital. Intervention(s) Controlled ovarian hyperstimulation, oocyte retrieval, in vitro fertilization, transmyometrial ET, MFPR procedure for triplet pregnancy. Patient(s) A 33-year-old patient with endometriosis-associated and tubal factor infertility who underwent uterovaginal canalization surgery for congenital cervical atresia 9 years ago. Main Outcome Measure(s) Successful delivery after transmyometrial ET followed by MFPR. Result(s) A total of three IVF cycles and four procedures of transmyometrial ET were performed. In the third cycle a triplet pregnancy was achieved. MFPR was performed 35 days after embryos transfer, two healthy babies delivered at 31 weeks gestation. Conclusion(s) With aggressive therapy, successful pregnancy is possible in similar patients.

Objective To assess the efficacy of human embryo twinning by blastomere biopsy at different early embryonic stages (splitting efficiency) and to determine the in vitro developmental capacity of twinned human embryos (developmental efficiency). Design Randomized comparative study. Setting Private IVF centers. Patient(s) Couples undergoing IVF donating triploid embryos. Intervention(s) Embryos at the 2- to 5- and 6- to 8-cell stage were split into twin embryos. Half the number of blastomeres from donor embryos were removed and inserted into recipient empty zonae pellucidae. After embryo splitting, donor and recipient embryos were cultured in vitro. Main Outcome Measure(s) Development of twinned embryos to the blastocyst stage. Result(s) The number of developing embryos obtained after splitting could be increased in comparison with the number of embryos available before splitting at the 6- to 8-cell stage but not at the 2- to 5-cell stage (splitting efficiency). Splitting of 6- to 8-cell embryos yielded superior rates of twin embryos developing to blastocysts (developmental efficiency). Twinning success was related to the superior morphological quality of embryos used for splitting. Conclusion(s) This is the first report on twinned human embryos developing to blastocysts. This study exhibits the potential for novel applications in human assisted reproduction.

Objective To determine the psychosocial risks associated with multiple births (twins or triplets) resulting from assisted reproductive technology (ART). Design Transverse study. Setting Infertility units of a university hospital and a private hospital. Patient(s) Mothers and fathers of children between 6 months and 4 years conceived by ART (n = 123). The sample was divided into three groups: parents of singletons (n = 77), twins (n = 37), and triplets (n = 9). Intervention(s) The questionnaire was self-administered by patients. It was either completed at the hospital or mailed to participants' homes. Main Outcome Measure(s) Scales measured material needs, quality of life, social stigma, depression, stress, and marital satisfaction. Result(s) Logistic regression models were applied. Significant odds ratios were obtained for the number of children, material needs, social stigma, quality of life, and marital satisfaction. The results were more significant for data provided by mothers than by fathers. Conclusion(s) The informed consent form handed out at the beginning of ART should include information on the high risk of conceiving twins and triplets and on the possible psychosocial consequences of multiple births. As soon as a multiple pregnancy is confirmed, it would be useful to provide information on support groups and institutions. Psychological advice should also be given to the parents.

Objective To present a case report of a unilateral triplet ectopic pregnancy (EP) conceived by IVF–embryo transfer. Design Case report. Setting University Hospital, Budapest, Hungary. Patient(s) A 26-year-old infertile woman with a history of right salpingectomy, hyperprolactinemia, and male factor infertility underwent IVF–embryo transfer of three embryos. Early transvaginal sonography revealed a triplet pregnancy in the left fallopian tube (two at interstitial and one at ampullary location). Intervention(s) Multiple dose methotrexate (MTX) therapy was applied. Main Outcome Measure(s) Follow-up pelvic ultrasounds and laboratory testing confirmed fetal cardiac activity cessation and decreasing β-hCG levels. Result(s) In spite of the decreasing β-hCG levels the tube's diameter increased, the patient's symptoms escalated, and finally, the level of hemoglobin and hematocrit decreased. Laparotomy was performed with the removal of the left tube and cornual part of the uterus. Conclusion(s) Our case represents a very rare condition, a unilateral triplet EP after IVF–embryo transfer—the first one ever reported in the literature. After IVF–embryo transfer early ultrasound examinations are important to identify EPs at an early stage when medical management can still be taken into consideration. Strict monitoring is necessary to identify the success of medical intervention or the need for surgery.

Objective To describe the first reported case of a triplet pregnancy subsequent to the use of an aromatase inhibitor for ovulation induction. Design Case report. Setting Academic medical center. Patient(s) A 32-year-old female with polycystic ovary syndrome and primary infertility. Intervention(s) Letrozole, 5 mg/day, on cycle days 2 to 6 for ovulation induction. Main Outcome Measure(s) Clinical pregnancy. Result(s) Viable triplet gestation. Conclusion(s) Use of an aromatase inhibitor for ovulation induction does not eliminate the risk for higher order multiple pregnancy.

Objective To describe a case of monozygotic triplet pregnancy following egg donation and the transfer of a single frozen-thawed embryo. Design Case report. Setting District general hospital and regional department of fetal medicine in northeast England. Patient(s) A 38-year-old woman with a 2-year history of primary infertility due to severe endometriosis and poor ovarian reserve who conceived after egg donation and transfer of a single frozen-thawed embryo. Intervention(s) Transfer of a single frozen-thawed embryo and delivery of three identical female infants by emergency caesarean section because of preterm labor at 32 weeks' gestation. Main Outcome Measure(s) Review of effect of assisted conception on monozygotic twinning rates. Result(s) Healthy outcome for all three infants. Conclusion(s) Assisted reproductive treatments may lead to disturbances in zona pellucida architecture and an increase in monozygotic twinning rates. Couples need to be informed of this and the increased risks associated with these pregnancies before they begin with treatment.

To evaluate the risks of pregnancy complications and adverse outcomes associated with increasing maternal age and higher plurality.Population-based, historic cohort study.US birth certificates and infant death certificates.Live births ofor =20 weeks gestation between 1995-2000: 22,991,306 singleton, 316,696 twin, and 12,193 triplet pregnancies.None.Pregnancy-associated hypertension, incompetent cervix, tocolysis, premature rupture of membranes, excessive bleeding at delivery, delivery29 weeks, and infant death.Compared to singletons, the risks for all adverse outcomes among multiple pregnancies were significantly elevated, and were highest for tocolysis, delivery29 weeks, and infant mortality. Within pluralities, increasing maternal age was associated with significantly higher risks of pregnancy-associated hypertension, excessive bleeding, and incompetent cervix, but for twin and triplet pregnancies, significantly lower risks for tocolysis (agesor =40, singleton adjusted odds ratio [AOR] 0.97, twin AOR 0.67, triplet AOR 0.72), delivery29 weeks (agesor =40, singleton AOR 1.55, twin AOR 0.72, triplet AOR 0.52), and infant mortality (agesor =40, singleton AOR 1.34, twin AOR 0.71, triplet AOR 0.42).Older maternal age and higher plurality are each associated with increasing risks for many pregnancy complications, but with significantly lower risks of tocolysis, early preterm birth, and infant mortality.

Objective To report on a patient with a monochorionic triamnionic triplet pregnancy after IVF with donor oocytes. Design Case report. Setting Academic tertiary care hospital. Patient(s) A 42-year-old woman who underwent IVF with donor oocytes. Intervention(s) After failed IVF attempts, the patient chose to undergo treatment with donor oocytes. Her 23-year-old oocyte donor underwent standard controlled ovarian hyperstimulation. Retrieved oocytes were fertilized in vitro, and two embryos were transferred at the blastocyst stage. Main outcome measure(s) Intrauterine pregnancy with single gestational sac and three fetal poles with cardiac activity. Result(s) After extensive counseling with perinatologists about pregnancy complications, the patient elected to terminate at 10 weeks of gestation. Conclusion(s) Several processes have been suggested to explain the increase in monozygotic twinning after IVF. These factors include advanced maternal age, superovulation, manipulation of the zona pellucida, and prolonged culture. It is possible that other factors may also play a role, especially in high-order monozygotic multiple pregnancies. All patients should be informed of the potential risk of a high-order multiple pregnancy after IVF, even when only one or two embryos are transferred.

Objective To report a case of successful triplet pregnancy in an acromegaly patient with IVF and embryo transfer. Design Case report. Setting Tertiary center for assisted reproductive technologies. Patient(s) A 33-year-old woman with acromegaly and primary infertility. Intervention(s) Controlled ovulation hyperstimulation and IVF/embryo-transfer treatment using gonadotropins. Main outcome measure(s) Uncomplicated pregnancy course and successful take-home triplet infant girls. Result(s) Successful ovarian stimulation and IVF is possible in acromegalic patients. Conclusion(s) There may be an effect of elevated growth hormone resulting in increased ovarian response to gonadotropin, inducing hyperstimulation and high-order multiple pregnancies in these patients.

Objective To investigate the impact of delaying the transfer of in vitro fertilized embryos to day 5 on embryo development by comparing serum β-hCG levels in pregnancies established after day 3 embryo transfers and those after day 5 blastocyst transfers at equivalent time intervals after fertilization. Design A retrospective analysis. Setting Assisted reproductive technology center in an academic research environment. Patient(s) Women who had an embryo transfer procedure performed after in vitro fertilization (IVF) at Northwestern University's IVF Program between January 1999 and December 2001 were included in this study. Intervention(s) Embryo transfer was performed either on day 3 or day 5 after oocyte retrieval for IVF (day 0), depending on the availability of good-quality embryos on day 3. Main outcome measure(s) Serum β-hCG concentrations determined 13 and 15 days after fertilization in pregnancies established by transferring cleavage-stage embryos on day 3 or blastocysts on day 5. Result(s) In singleton pregnancies, serum β-hCG concentrations were 75 ± 54 (mean ± SD, n=203) or 62 ± 41 (n = 109) IU/mL after day 3 or day 5 transfers, respectively. In twin pregnancies, the β-hCG concentrations were 162 ± 105 (n = 52) or 109 ± 55 (n = 49) after day 3 or day 5 transfers, respectively. The percentage increases in β-hCG concentrations between the first and second measurements were similar in the two groups (day 3: 144 ± 109, day 5: 142 ± 63, not statistically significant). Conclusion(s) Initial β-hCG concentrations in pregnancies resulting from day 5 transfers were lower than those from day 3 transfers when assessed at equivalent intervals from fertilization. This suggests that embryo development or implantation may be impaired by the additional 2 days in culture.

Objective To determine the genotype of a triplet resulted from an IVF procedure, with discordant cystic fibrosis (CF) phenotype. Design Molecular diagnosis of CF. Setting Affected triplet followed at the CF Clinic Center of Children's Hospital Los Angeles was referred to Molecular Genetics Laboratory at Georgetown University Medical Center for comprehensive DNA analysis of the cystic fibrosis transmembrane regulator ( CFTR ) gene. Patient(s) Three affected children and the healthy parents with negative family history of CF. Main outcome measure(s) Temporal temperature gradient gel electrophoresis and direct DNA sequencing were used to detect and to identify the mutations. Result(s) The child with classic CF had ΔF508 and R553X mutations. Two children with mild CF symptoms had ΔF508 and R117C. The father carried two mutations, R553X and R117C. The mother is a carrier for ΔF508. Conclusion(s) Mutational analysis of the CFTR gene should always be recommended to the infertile couples seeking for IVF. The CFTR mutation screening would be essential if the man has congenital bilateral absence of vas deferens (CBAVD) despite the negative family history of CF. Option of complete CFTR gene analysis at a cost of about $1,500–$2,000 should be made available if one mutation is found in the male partner with congenital bilateral absence of vas deferens.

To examine the results of a 3-year trial using blastocyst cryopreservation to limit multiple pregnancy and optimize overall pregnancy per cycle.Retrospective clinical evaluation of pregnancy rates after freezing and thawing human blastocysts.Tertiary-care academic center.Seven hundred fifty-three different patients treated in 783 IVF cycles with blastocysts frozen from July 2000 to June 2003.Two thousand, two hundred fifty-nine blastocysts were frozen in cycles in which only blastocysts were cryopreserved (cycles with pronuclear stage oocytes or pre-embryos also cryopreserved were excluded from the analysis). Of these, 628 (27.6%) were thawed in 218 cycles.Pregnancy rate per cycle with thaw.Four hundred seventy-nine (76.3%) blastocysts survived thawing, and 440 (92.0%) were transferred after exhibiting evidence of survival (most commonly, blastocoele reexpansion). In cycles with a thaw, 211 (96.8%) of 218 underwent intrauterine transfer. An average of 2.09 blastocysts was transferred per replacement. One hundred twenty-five (59.2%) clinical pregnancies were established, which included 23 sets of twins and 5 triplet gestations. Two sets of monozygotic twins were identified after the replacement of a single thawed blastocyst (1.6%). The age of the patient at the time of cryopreservation (37 years) was an important factor in the establishment of clinical and ongoing pregnancy. The mode of ovarian stimulation, replacement method, and whether blastocysts were frozen on day 5 or day 6 of development did not demonstrate clinical significance.Cryopreserved and thawed blastocysts demonstrated a similar potential for implantation when compared with fresh pre-embryos on day 3. On the basis of these results, the blastocyst stage of development appears to be optimal for clinical freeze-thaw trials.

On a national basis, the ratio of multiple births to total births tended to lessen in 1999 and 2000 compared to previous years (the good news), although in each of these years, the ratio of all multiple births compared to total births continued to increase (the bad news) (Fig. 1). However, values appear to vary considerably from state to state. For example, in Virginia, the increase in the ratio of multiple births to total births was smaller in 1999 than in previous years, but the steep upward trend continued for the year 2000 (Fig. 2).

Objective: To explore a possible mechanism of the increasing incidence of monozygotic twins following assisted hatching of human embryos. Design: Case report. Setting: Clinical research center in a medical school teaching hospital. Patient(s): A 37-year-old infertile woman with repeated IVF failures. Intervention(s): Assisted hatching of the day 3 embryos using acidic Tyrode's solution. Main Outcome Measure(s): The morphology of the zona-drilled embryos and the pregnancy outcome. Result(s): After assisted hatching, a herniated blastomere through an oversized opening in the zona pellucida was found in one embryo. The transfer of two zona-drilled embryos resulted in a triplet pregnancy. Conclusion(s): Large openings in the zona pellucida following chemically assisted hatching may cause premature hatching of the blastomeres and may be implicated in the occurrence of monozygotic twins.

Objective: To investigate the course of pregnancy and fetal outcome after first-trimester multifetal pregnancy reduction (MFPR) in patients with triplet pregnancies and uterine bleeding. Design: Case series of patients with threatened triplet pregnancies considered for MFPR. Setting: Department of Obstetrics and Gynecology, Rabin Medical Center, Petah-Tiqva, Israel. Patient(s): Forty-two patients with triplet pregnancies and first-trimester uterine bleeding. Intervention(s): At 10–15 weeks' gestation, MFPR with intracardiac injection of potassium chloride was performed. The procedures were performed 7–10 days after cessation of bleeding (9–13 weeks) or in the presence of minimal uterine bleeding (14–15 weeks). In patients with heavy uterine bleeding, MFPR was postponed. Main Outcome Measure(s): Early- and late-pregnancy complications related to the procedure, pregnancy outcome, and fetal survival. Result(s): Performance of MFPR at 14–15 weeks was associated with a higher abortion rate (38.5%), lower mean gestational age at delivery (30.6 weeks), and lower mean twin birth weight (1,376 ± 218 g and 1,014 ± 202 g) than was performance of MFPR at 10–13 weeks (18.8%, 33.2 weeks, and 1,720 ± 245 g and 1,596 ± 170 g, respectively). Abortion occurred in four of the five patients with moderate to heavy uterine bleeding who did not undergo MFPR; the fifth patient gave birth prematurely at 28 weeks, and two of the newborns died. Conclusion(s): Pregnancy outcome and fetal mortality and morbidity in triplet pregnancy after MFPR are directly correlated with duration and amount of first-trimester bleeding.

Objective: To report a triplet pregnancy that occurred after intracytoplasmic injection of sperm into cryopreserved oocytes. Design: Case report. Setting: Instituto de Ginecologia y Fertilidad (IFER), Buenos Aires, Argentina. Patient: A 36-year-old infertile patient with premature ovarian failure and a previous term pregnancy with fresh donated oocytes. Intervention(s): We administered leuprolide acetate for pituitary down-regulation followed by E 2 valerianate in incremental doses until an endometrial lining of >8 mm was observed by ultrasound. Thawing of frozen donated oocytes, intracytoplasmic sperm injection (ICSI), and translaparoscopic fallopian tube ET also were performed. Natural micronized progesterone was administered intravaginally (600 mg/d) before ET. Main Outcome Measure(s): Ultrasound at the 8th week of gestation revealed a triplet pregnancy with active fetal heartbeats. Result(s): A triple intrauterine gestation was achieved with the use of microinjection into cryopreserved oocytes. Conclusion(s): This case illustrates the feasibility of oocyte cryopreservation for clinical use in the era of ICSI.

Objective: To assess the mental health of mothers of triplets and the quality of relationship with the children 4 years after delivery. Design: Prospective follow-up study from delivery to 4 years. Assessments at home by a psychologist, using semistructured tape-recorded interviews. Setting: One maternity hospital in Paris, France. Patient(s): Eleven consecutive mothers having delivered triplets between October 1988 and February 1990. All except one had conceived after infertility treatment. Main Outcome Measure(s): Evaluation of the mothers' emotional well-being and level of depression measured by the CES-D Scale (Center for Epidemiologic Studies-Depression Scale). Opinion of the mothers about the quality of the relationship with the children. Result(s): All mothers reported emotional distress at 4 years, mainly fatigue and stress. Four mothers had a high score of depression and used psychotropic medication. The relationship with the children and difficulties in coping with their aggressive behavior and conflicts were the main reason for psychological distress. Difficulties had not decreased since the previous assessment at 2 years. Four mothers spontaneously expressed regrets about having triplets. Conclusion(s): Patients undergoing infertility treatments should receive adequate information about the long-term psychological "cost" of a triplet birth. Infertility treatments should be adapted in order to decrease the risk of triplet pregnancies.

OBJECTIVES: To describe a rare case of triplet cornual pregnancy after IVF-ET and to assess the role of magnetic resonance imaging (MRI) for early diagnosis. DESIGN: Case report. SETTING: Infertility and IVF Unit, in an university medical center. PATIENT: A 31-year-old healthy patient with a 3-year history of primary male infertility. INTERVENTION: Standard IVF-ET treatment cycle, using a GnRH-agonist (long protocol) and hMG for ovarian stimulation. RESULTS: A cornual triplet pregnancy is described with the approach for the diagnosis. Magnetic resonance imaging was complementary to endovaginal sonography for early diagnosis and permitted a timed conservative management. CONCLUSIONS: When transvaginal ultrasound findings did not provide an accurate location of the pregnancy, MRI was indicated to confirm the diagnosis.

Objective To assess the incidence of spontaneous embryo reduction as well as the obstetric and neonatal outcome of triplet gestations after assisted reproductive techniques (ART). Methods We analyzed the spontaneous outcome of 38 pregnancies in which three gestational sacs were identified with vaginal ultrasound between 21 and 28 days after ART. Weekly follow-up visits were scheduled during the first trimester until referral to a high-risk obstetrician. After delivery, each patient was interviewed individually and, if necessary, the obstetrician was contacted. Results The triplets delivery rate was 47.4%, whereas 31.6% delivered twins, 18.4% delivered singletons, and only one patient miscarried all three sacs (2.6%). Finding three fetal heart beats was associated with a triplet delivery rate of 69.2%, a twin incidence of 19.2%, and a singleton birth rate of 11.6%. Embryo resorptions were observed mainly during the first 7 weeks of gestation and did not occur beyond the 14th week. The mean gestational age at delivery and neonatal birth weight were significantly lower among triplets (32.8 weeks and 1,740 g versus 35.3 weeks and 2,352 g in twins and 39.1 weeks and 3,122 g for singletons). Triplets had a 100% prematurity and cesarean section rate compared with 67% and 75% in twins and 0% and 43% in singletons, respectively. Hospitalization at the Neonatal Intensive Care Unit was required in 83% of newborn triplets, 29% of twins, and 0% of singletons, with a mean stay of 34 and 21 days for triplets and twins, respectively. One stillbirth and no neonatal deaths were reported, with an overall perinatal mortality rate of 11.9 per 1,000. Conculsion Spontaneously, approximately 50% of triplet pregnancies will experience at least one embryo resorption. The ongoing triplets demand a complex and more expensive perinatal management, a strong argument to consider limiting the number of oocytes-embryos transferred in ART.

Objectives To describe an extremely rare anomaly in an infant born after IVF-ET, and to assess its possible relationship to the artificial reproductive technology. Design Case report. Setting Infertility and IVF Unit, in a tertiary academic medical center. Patient A 31-year-old healthy patient with a 9-year history of secondary, unexplained infertility. Intervention Standard IVF-ET treatment cycle, using GnRH-a (short protocol) and hMG for controlled ovarian hyperstimulation. Results Poland anomaly (asymmetric thorax with absence of the right pectoralis major muscle, low set rudimentary right nipple, and very mild hypoplasia of the right upper limb) is described for the first time in an infant who is one of a trizygotic triplet after IVF treatment. Conclusions In view of the currently held hypothesis concerning the pathogenesis of Poland anomaly, the possibility of a teratogen or an event related to the reproductive procedure as the cuase of this anomaly seems unlikely.

Objective: To describe selective embryo reduction of two triplet pregnancies with a monozygotic twin. Design: Case reports. Setting: Infertility unit of a Department of Obstetrics and Gynecology. Patient(s): Two patients treated with IVF-ET who had triplet pregnancies. Intervention(s): Selective embryo reduction of monozygotic twins. Main Outcome Measure(s): Fetal heart beat. Result(s): During intracardiac injection of potassium chloride plus midazolam in one of the monozygotic twin fetuses, we observed an immediate diminution of the cardiac pulse rate of the second twin. This phenomenon was observed in both patients. Conclusion(s): These observations clearly indicate the presence of vascular anastomosis between the two fetuses of these monozygotic twins. Thus, use of toxic substance to reduce one of the two fetuses of a monozygotic twin pregnancy is contraindicated. In cases of triplets that include a monozygotic twin, it is safest to interrupt the evolution of the twin if selective reduction is desired.

Objective To compare the effect of fertility drugs and IVF on the outcome of triplet pregnancies. Design Prospective clinical study. Setting A single university medical center. Patients One hundred six consecutive triplet pregnancies treated from 1984 through 1992. Main Outcome Measures The frequency of pregnancy loss, livebirths, and antenatal and neonatal complications was compared in spontaneous, clomiphene citrate (CC), menotropins, and IVF triplet pregnancies. Results Eighty-one of the 106 (76.4%) triplet pregnancies progressed beyond 25weeks, comprising 6 of 7 (85.7%) spontaneous pregnancies, 13 of 16 (81.2%) CC induced, 44 of 56 (78.6%) menotropin induced, and 18 of 27 (66.6%) IVF gestations. There were no significant differences in the stillbirth and neonatal mortality rates according to the mode of conception. The mean gestational ages and the mean birth weights were similar in the four groups. The frequency of premature contractions, premature rupture of membranes, cesarean section, and neonatal complications were similar in the ovulation induction and IVF pregnancies. Conclusion Triplet pregnancies after ovulation induction and IVF have a similar outcome.

To review the maternal morbidity and neonatal morbidity and mortality associated with in vitro fertilization (IVF) multiple pregnancies.Retrospective analysis of data collected from office and hospital records and from questionnaires sent to patients, their obstetricians, and pediatricians.Patients (all with private insurance carriers) enrolled in an academic IVF program (The Jones Institute for Reproductive Medicine).All IVF pregnancies resulting in one or more gestational sacs on the initial ultrasound at 6 to 7 weeks were reviewed.The frequency and severity of obstetrical and neonatal complications and the perinatal mortality of IVF twins, triplets, and quadruplets were compared. These were also compared with non-IVF multiple pregnancies.From 1982 to 1990, 629 IVF pregnancies progressed beyond 20 weeks; 115 twins (18.3%), 15 triplets (2.4%), and 4 quadruplets (0.6%). There was a high incidence of antenatal complications such as abortions (30.3%, 42%, and 20%), premature labor (41.5%, 92.3%, and 75%), pregnancy-induced hypertension (17.0%, 38.6%, and 50%), and gestational diabetes mellitus (3.1%, 38.5%, and 25%) for twins, triplets, and quadruplets, respectively. The mean gestational age at delivery was 35.5 +/- 3.7, 31.8 +/- 2.7, and 31.0 +/- 1.7 weeks, respectively. There was also a proportionate progressive increase in neonatal complications. The mean weights were 2,473 +/- 745, 1,666 +/- 441 and 1,414 +/- 368 g, respectively. Twins (22.7%), 64.1% of triplets, and 75% of quadruplets needed admission to the neonatal intensive care unit and remained for an average of 12.0 +/- 2.3, 17.4 +/- 14.0, and 57.8 +/- 17.9 days, respectively. There was no difference in the mean Apgar scores or the incidence of congenital malformations in the three groups. The corrected perinatal mortality rates were 38.5, 0.0, and 0.0 per thousand live births, respectively.Triplet and quadruplet IVF pregnancies have increased obstetrical and neonatal complications compared with IVF twins. The perinatal mortality and the incidence of congenital malformations are, however, comparable in all three groups.

Objective To report a possible association between intracytoplasmic sperm injection (ICSI)–preimplantation genetic diagnosis (PGD) and monozygotic multiple gestation. Design Small case series. Setting In vitro fertilization unit in an academic medical center. Patient(s) Three patients were treated with ICSI-PGD for sexing as well as selection against a known translocation. Intervention(s) Transfer of day 4 embryos to the uterus. Main Outcome Measure(s) Clinical pregnancy. Result(s) Two pairs of monozygotic twins and a triplet pregnancy. Conclusion(s) Repeated manipulation of the zona pellucida as well as extended embryo culture during ICSI-PGD treatments may result in monozygotic twin and triplet pregnancies.

Objective To report a dichorionic quadramniotic quadruple gestation with monochorionic triamniotic triplets after intracytoplasmic sperm injection (ICSI) treatment and transfer of two embryos. Design Case report. Setting Academic reproductive medicine center. Patient(s) A 28-year-old nulligravida who underwent first ICSI cycle. Intervention(s) After 4 years of primary infertility for andrologic subfertility, the patient underwent her first ICSI cycle, with transfer of two fresh embryos on day 3. Main Outcome Measure(s) Transvaginal sonogram performed at 5 weeks after embryo transfer showed a dichorionic quadramniotic quadruple gestation with monochorionic triamniotic triplets and a singleton. Result(s) After extensive counseling, the couple decided to proceed to a selective reduction of two of monochorionic triamniotic triplets and a twin pregnancy remained. Fetal reduction was successfully performed by intracardiac puncture and aspiration at 5 + 3/7 weeks after embryo transfer. Two healthy baby girls were born. Conclusion(s) Several factors have been suggested to explain the increase in monozygotic multiple pregnancies after assisted reproductive technique (ART): advanced maternal age, superovulation, and manipulation of the zona pellucida (ZP) including ICSI and assisted hatching, prolonged culture, and in vitro culture condition. All patients should be informed that monozygotic multiple pregnancies occur at a significantly higher rate after ART procedures and could be an important complication after IVF-ICSI treatment.

Objective To describe an exceptional case of conjoined twins in a triplet pregnancy after intracytoplasmic sperm injection (ICSI) and blastocyst transfer. Design Case report. Setting University teaching hospital reproductive endocrinology department and infertility practice. Patient(s) A 34-year-old woman underwent ICSI and received two blastocysts transferred. Intervention(s) Transvaginal ultrasonography performed sequentially during early pregnancy. Main outcome measure(s) Ultrasound images of the fetus in gestational sac. Result(s) Two gestational sacs in the uterus were revealed at the 5th week. At the 8th week of gestation, a single fetus was seen in one sac, whereas thoracopagus conjoined twins was diagnosed in the other sac. At the 10th week, the conjoined twins had a spontaneous cardiac arrest confirmed by color Doppler. The subsequent course was uneventful, and a healthy child was born at 39th week. Conclusion(s) To date, a small number of cases of conjoined twins in IVF/ICSI pregnancies have been reported, in which most cases were treated with manipulations causing possible trauma in the zona pellucida. Our case is unique in that the transferred embryos were blastocysts that might have had additional damage on the zona pellucida from the longer culture.

To our knowledge, this is the first case report of three pregnancies resulting from the one batch of embryos. As the survival rate for cryopreserved embryos increases, there will be more families that will be able to be completed after just one cycle of hyperstimulation and oocyte collection, thereby making IVF-ET more cost-effective.

Objective To report the first dichorionic triamniotic triplet pregnancy discordant for trisomy 13 after in vitro fertilization (IVF) treatment with preimplantation genetic screening (PGS). Design Case report. Setting Private IVF center. Patient(s) A 40-year-old para 1+6 woman. Intervention(s) IVF combined with PGS for chromosomes 13, 16, 18, 21, and 22, resulting in the transfer of two embryos. Main Outcome Measure(s) Prenatal fetal ultrasonography revealed a dichorionic triamniotic triplet pregnancy. An amniocentesis, performed at 15-weeks' gestation, confirmed that the singleton and one monozygotic twin were normal but the other monozygotic twin was trisomy 13. Result(s) After diagnosis and counseling, selective termination of the trisomy 13 monozygotic twin was performed at 16 weeks and 4 days. At 18 weeks and 4 days the co-twin died. A healthy boy was delivered by elective caesarean section at 36–weeks' gestation. Conclusion(s) Assisted reproductive techniques that breach the embryo's zona pellucida such as assisted hatching and PGS embryo biopsy increase the incidence of monozygotic twins. Due to high levels of mosaicism in human preimplantation embryos, PGS cannot ensure that embryos diagnosed as normal and selected for transfer do not contain abnormal cells. Hence, further reports of discordant monozygotic twins following PGS are expected, emphasizing the need for appropriate counseling of patients wishing to embark on an IVF/PGS treatment cycle.

Objective To report a case of triplet pregnancy after metformin treatment only, in a woman with polycystic ovary syndrome (PCOS) and a family history of twin pregnancies. Design Case report and literature review. Setting Gynecologic endocrinology clinic, tertiary federal hospital. Patient(s) A white, lean, 34-year-old woman, treated for PCOS since age 28, who had tried to conceive spontaneously for 6 months, with no evidence of ovulation. Intervention(s) Metformin, 850 mg, for 1.5 months. Main Outcome Measure(s) Pregnancy (triplet). Result(s) Pregnancy developed up to premature labor at 31 weeks. The patient delivered two boys and one girl, in need of neonatal intensive care for 33 to 44 days. Conclusion(s) Despite the paucity of literature data, we believe that metformin, when associated with predisposing therapies or conditions, may facilitate high-order pregnancies.

Objective: To report the first case of fetal malformation after preimplantation diagnosis for Duchenne muscular dystrophy (DMD). Design: Case report. Setting: Perinatal center in a university hospital. Patient(s): A conductor for DMD in her third pregnancy. Intervention(s): Preimplantation diagnosis was performed in an outside hospital. In our center, a dichorionic triplet pregnancy with acardius acranius was diagnosed. The anastomosis between the "pump"-twin and the fetus with acardius was embolized with histoacryl to prevent worsening cardiac insufficiency of the "pump"-twin. Main Outcome Measure(s): Pregnancy outcome. Result(s): The anastomosis between the "pump"-twin and the fetus with acardius was occluded successfully. Premature preterm rupture of membranes led to rapid labor and delivery at 24 + 5 weeks' gestation. The smaller girl died of severe hyaline membrane disease, whereas the other infant had no major clinical problems and has developed well. Conclusion(s): There might be an association between embryo biopsy and fetal malformations. The setting up of a birth register after embryo biopsy is strongly recommended.

To our knowledge, this represents the first case of a laparoscopically treated triplet EP and the first time that a double EP in the same tube was treated conservatively (with preservation of the tube). Multiple EPs may be more common than currently thought, and our report offers an alternative explanation for at least some cases of persistent EP after conservative surgical therapy. Finally, given the substantial cost savings and reduced postoperative recovery time associated with operative laparoscopy, when the patient is stable and the surgeon experienced, the laparoscopic approach should be tried, regardless of the number of EPs or their size.

The growth of the mean gestational sac diameter and the crown-rump length were evaluated from individual series and found to be linear in singletons, twins, and triplets from an in vitro fertilization program as well as in pregnancies with ovulation determined from serial ultrasound folliculograms. No difference in growth rate between the different groups was observed. The 95% confidence limits were 7.7 days before and 7.5 days after mean for the gestational sac diameter, and 5.2 days before and 5.6 days after mean for the crown-rump length. These limits, used together with new linear equations, create less anxiety and less unnecessary surgical intervention than current nonlinear standards when conceptual age is known and the gestational sac or the crown-rump length are too small to be measured.