High-order Multiple Pregnancy Rates Research Articles

Small-sized follicles could contribute to high-order multiple pregnancies: outcomes of 6552 intrauterine insemination cycles.

Can predictors of twin and high-order multiple pregnancy among women with multiple cycles of ovarian stimulation intrauterine insemination (IUI) be identified? Retrospective cohort study of IUI cycles carried out between January 2014 and December 2015 in a private clinic in Spain. The 4879 women and 6552 cycles analysed in this study include single IUI with ovarian stimulation using recombinant FSH. Number of follicles and follicle size were the only factors with a significant effect (P < 0.001) on the likelihood of achieving a twin or multifetal pregnancy. Follicles 12 mm or wider greatly increase the chances of achieving a twin or multifetal pregnancy. A total of 73 out of 127 (57.5%) twin pregnancies occurred in cycles with at least one additional follicle measuring 12 mm or wider, and 102 out of 127 twin pregnancies (80.3%) occurred in cycles with at least one additional follicle measuring 14 mm or wider. Cancellation criteria should consider the presence of follicles 12 mm or wider. Follicles measuring 12 mm or wider increase the risk of having a twin or a high-order multiple pregnancy rate. These data may help clinicians balance decision-making between cancelling and performing the cycle within an IUI procedure.

Ovulation induction outcomes: analysis of more than 1500 cycles

OBJECTIVE: To evaluate the outcomes of a large cohort of patients undergoing ovulation induction cycles.DESIGN: A retrospective cohort study of 1525 ovulation induction cycles performed in 694 patients between August 1998 and December 2008.MATERIALS AND METHODS: Patients underwent ovulation induction cycles with gonadotropins then timed intercourse or intrauterine insemination. Clomiphene citrate or a GnRH antagonist were used in about 10% of the cycles. Strategies used to reduce multiple gestations included low gonadotropin doses, and cancellation in high risk patients for more than three follicles > 16 mm or high estradiol levels.RESULTS: Per cycle pregnancy rate was 12.4% with a per cycle live birth rate of 7.5%. There was a trend towards higher per cycle pregnancy rate and live birth rate in younger patients (P=.0002). Multiple pregnancy rate was 12.7% with 10.1% twins and 2.6% triplets. Miscarriage rate was 25.8%, after excluding biochemical pregnancies, with a trend towards decreased miscarriages in younger patients (P=.004). The use of a GnRH antagonist decreased the risk of miscarriage (AOR .26, 95% CI .07-.91). Patients with hypothalamic ovarian dysfunction were associated with the highest per cycle pregnancy rate and live birth rate of 37.5% (no miscarriages) followed by PCOS. The lowest per cycle live birth rates were in women with diminished ovarian reserve, recurrent miscarriages, and uterine myomas (2%). The birthweight of a singleton from a pregnancy with a vanishing twin (n=8) was significantly lower than the birthweight of a singleton without a vanishing twin (2882 gm vs 3250gm, P=.013).CONCLUSIONS: Reducing multiple pregnancy with ovulation induction remains an important and challenging goal although there are no strict universal guidelines. In this cohort of patients, the high order multiple pregnancy rate was limited to 2.6% by using certain strategies. Risks of multiple pregnancy include a lower birthweight of the surviving singleton originating from a twin pregnancy. OBJECTIVE: To evaluate the outcomes of a large cohort of patients undergoing ovulation induction cycles. DESIGN: A retrospective cohort study of 1525 ovulation induction cycles performed in 694 patients between August 1998 and December 2008. MATERIALS AND METHODS: Patients underwent ovulation induction cycles with gonadotropins then timed intercourse or intrauterine insemination. Clomiphene citrate or a GnRH antagonist were used in about 10% of the cycles. Strategies used to reduce multiple gestations included low gonadotropin doses, and cancellation in high risk patients for more than three follicles > 16 mm or high estradiol levels. RESULTS: Per cycle pregnancy rate was 12.4% with a per cycle live birth rate of 7.5%. There was a trend towards higher per cycle pregnancy rate and live birth rate in younger patients (P=.0002). Multiple pregnancy rate was 12.7% with 10.1% twins and 2.6% triplets. Miscarriage rate was 25.8%, after excluding biochemical pregnancies, with a trend towards decreased miscarriages in younger patients (P=.004). The use of a GnRH antagonist decreased the risk of miscarriage (AOR .26, 95% CI .07-.91). Patients with hypothalamic ovarian dysfunction were associated with the highest per cycle pregnancy rate and live birth rate of 37.5% (no miscarriages) followed by PCOS. The lowest per cycle live birth rates were in women with diminished ovarian reserve, recurrent miscarriages, and uterine myomas (2%). The birthweight of a singleton from a pregnancy with a vanishing twin (n=8) was significantly lower than the birthweight of a singleton without a vanishing twin (2882 gm vs 3250gm, P=.013). CONCLUSIONS: Reducing multiple pregnancy with ovulation induction remains an important and challenging goal although there are no strict universal guidelines. In this cohort of patients, the high order multiple pregnancy rate was limited to 2.6% by using certain strategies. Risks of multiple pregnancy include a lower birthweight of the surviving singleton originating from a twin pregnancy.

Mathematical model prospectively halves the high-order multiple pregnancy rate

To evaluate the accuracy of a mathematical embryo selection model in predicting pregnancy and high-order multiple pregnancy (triplets or greater) and to determine this model's impact on high-order multiple pregnancy rates in our IVF program. A prospective study. The details of our model was previously published (Torsky 2005). Briefly, each embryo was assigned to a group based on the number of cells and embryo grade. Initially, probability of not causing pregnancy (Q) was computed for each group. Pregnancy probability (P) was then determined, P=1 – Q. The final equation was as follows: We transferred a cohort of embryos (4 or less) with the highest pregnancy probability at 10% or less high-order multiple pregnancy probability. Embryos were prospectively selected solely based on our model in 117 consecutive non-donor fresh IVF cycles. All patients underwent the same stimulation protocol. Student's t-test and stepwise logistic regression were used for statistical analyses. Of 117 women, 48 (41%) achieved pregnancy. There were 5 (10%) high-order multiple pregnancies. The mean age, number of oocytes retrieved and number of embryos transferred were similar between pregnant and non-pregnant groups. Sensitivity and specificity of our mathematical model for high-order multiple pregnancy were 40% and 84%, respectively. Negative predictive value was 97%. Stepwise logistic regression analysis selected our model as the best predictor of high-order multiple pregnancy (LR 3.55, P=0.05). Sensitivity and specificity of our model for any pregnancy were 42% and 72%. Stepwise logistic regression revealed our model to be the best predictor of pregnancy (LR 3.96, P<0.05). This is the first study reporting prospective use of a mathematical model to select a cohort of embryos. Our model was the best predictor of pregnancy and high-order multiple pregnancy compared to age, number of oocytes retrieved and number of embryos transferred. After we implemented the model in our clinical practice, our high-order multiple pregnancy rate was decreased by about 50%. It declined from 23% to 10% while maintaining similar pregnancy rates (43% vs. 41%).

Assisted reproductive technology practice patterns and the impact of embryo transfer guidelines in the United States

[1] To evaluate trends in number of embryos transferred and resultant high-order multiple (HOM) pregnancy rates by Society for Assisted Reproductive Technology (SART)-member clinics between 1996 and 2003 and [2] to relate these practice patterns and outcomes to clinic compliance with SART-American Society for Reproductive Medicine (ASRM) embryo transfer guidelines. Retrospective. Society for Assisted Reproductive Technology-member fertility centers in the United States. Five hundred thirty-six thousand, five hundred twenty-four fresh, nondonor IVF cycles. None. Number of embryos transferred; pregnancy rates; implantation rates; and proportion of singleton, twin, and HOM pregnancies. The number of embryos transferred declined each year. High-order multiple pregnancy rates also declined, whereas the twin rates remained stable. The most pronounced declines in number transferred occurred immediately after publication of SART-ASRM embryo transfer guidelines. After stratifying clinics according to mean and modal number of embryos transferred, clinics transferring the fewest embryos in women <35 years of age had the highest mean implantation and pregnancy rates. Furthermore, the percentage of clinics transferring two embryos to a majority of women <35 years of age increased from 3.3% in 1996 to 49.9% in 2003. The implementation of SART-ASRM embryo transfer guidelines is associated with significant reductions in the number of embryos being transferred, along with reductions of HOM pregnancies. Initiatives to further reduce twin pregnancies and encourage singleton gestation outcomes are outlined.

Improvements achieved in an oocyte donation program over a 10-year period: sequential increase in implantation and pregnancy rates and decrease in high-order multiple pregnancies

To compare outcome parameters and cumulative pregnancy rates (PRs) in oocyte donation cycles over a period of 10 years. Retrospective study. University-affiliated assisted reproductive technology program. Women undergoing oocyte donation (10,537 cycles) between 1995 and 2005. Ovarian stimulation and oocyte retrieval in donors. Embryo transfer performed in recipients after endometrial preparation. Outcome parameters and cumulative PRs were calculated and compared in relation to indication, age, and origin of sperm used. Overall PR, implantation rate, clinical PR, and miscarriage rate per embryo transfer performed were 54.9%, 27%, 50.3%, and 19%, respectively. Ongoing PR per transfer was 40.2%, and twin and high-order multiple PRs were 39% and 6%, respectively. Mean number of embryos transferred was reduced from 3.6 +/- 0.8 to 1.9 +/- 0.3, implantation rate improved from 16.7% to 38.3%, and ongoing PR improved from 31% to 44.3%. Cumulative PRs did not differ significantly among different indications for oocyte donation, age groups, or origin of sperm used for oocyte insemination. Overall cumulative PRs after three and five cycles were calculated as 87% and 96.8%, respectively. Significant improvements in outcome parameters were achieved within 10 years. Similar cumulative PRs were observed regardless of recipient age, indication for oocyte donation, or sperm origin.

O-85: ART practice patterns and the impact of embryo transfer guidelines in the United States

O-85: ART practice patterns and the impact of embryo transfer guidelines in the United States

Use of outcomes-based data in reducing high-order multiple pregnancies: the role of age, diagnosis, and embryo score

Objective To identify high-risk categories for high-order multiple pregnancy (HMP) in in vitro fertilization (IVF), establish clinic-specific HMP risk data for counseling use, and verify their utility in reducing HMP. Design Before and after intervention study. Setting Two IVF programs using the same embryology laboratory and IVF protocols. Patient(s) All IVF patients undergoing fresh embryo transfers. Intervention(s) Use of clinic-specific age, diagnosis, and embryo score (ES) risk data in assessing individual HMP risk during informed consent. Main outcome measure(s) HMP and pregnancy outcomes. Result(s) In determining clinic-specific high risk categories and developing outcomes-based HMP risk data for counseling, the good outcome rate (GR) was defined as the percentage of singleton or twin deliveries per cycle and the bad outcome rate included no pregnancy or nondelivered pregnancies (miscarriages, multifetal reduction) and HMP per cycle. During 1995 to 1999, age <35 years, calculated morphologic ES, and donor egg (DE) cycles were factors shown by logistic regression to statistically significantly affect the GR. The optimal GRs for DE <35 and ≥35 years (donor age), and non-DE cycles <35 years were achieved with two (57.7%), three (43.2%), and three (43.2%) embryos transferred, respectively. A DE <35 years with ≥3 embryos transferred had the highest risk for HMP. The GR correlated (0.91) with the ES according to the formula: GR = 3.3 + 2.0 ES, when ES range was between 4 and 26. Clinic-specific risks for HMP based on age, diagnosis, and ES were developed and considered while counseling for ET during 2004. The clinic-specific HMP risk data made for a reduction in the HMP rate of 90.9% for DE-IVF (11.8% to 1%) and 53.8% for all IVF (9.1% to 4.2%), without decreases in clinical pregnancy or delivery rates. Physicians showing the greatest decline (64%) in HMP had no reduction in pregnancy or delivery rates. Conclusion(s) The use of clinic-specific HMP risk data in counseling based on age, diagnosis, and ES provided a 53% to 64% reduction in HMP without affecting rates of pregnancy or delivery. The clinic-specific ES system correlated closely with good outcomes. A standardized ES system may provide useful information for counseling during ET informed consent.

Clomiphene citrate intrauterine insemination (IUI) before gonadotropin IUI affects the pregnancy rate and the rate of high-order multiple pregnancies

Objective To determine if previous treatment with clomiphene citrate intrauterine insemination (CC-IUI) affects pregnancy and high-order multiple pregnancy (HOMP) rates in subsequent hMG-IUI or FSH-IUI cycles. Design Retrospective cohort study. Setting Private infertility clinic. Patient(s) Five hundred fifty-one patients (age <38 years) without tubal factor infertility, treated with 918 cycles of hMG/FSH-IUI after one or more unsuccessful cycles of CC-IUI; 908 patients treated with 1459 cycles of hMG/FSH-IUI without prior CC-IUI. Intervention(s) CC-IUI, hMG-IUI, FSH-IUI. Main outcome measure(s) Pregnancy rate per cycle, HOMP (three or more gestational sacs). Result(s) Pregnancy rates during the first three hMG-IUI or FSH-IUI cycles averaged 21.8 ± 1.1% without previous CC-IUI, 19.6 ± 1.3% after one to four cycles of CC-IUI, and 3.6 ± 2.6% after ≥ five previous CC-IUI cycles. The HOMP rates were 8.8% without previous CC-IUI, 7.5% after one, 5.7% after two and <2.6% (0 out of 38) after ≥ three previous CC-IUI cycles. Conclusion(s) Pregnancy rates in hMG/FSH-IUI cycles are significantly reduced after four unsuccessful CC-IUI cycles. High-order multiple pregnancies due to hMG/HMG-IUI are reduced following previous unsuccessful CC-IUI cycles.

Stimulated Intrauterine Insemination: Efficient, cost-effective, safe?

A retrospective report of pregnancy and birth rates achieved in 1010 cycles of stimulated intrauterine insemination (SIUI). Over the years there has been an increasing emphasis on safety, particularly towards reducing the number of high order multiple pregnancies. SIUI is a complex form of assisted conception and requires a high level of clinical judgement to maintain an optimal balance between maximising pregnancy and birth rates and minimising complications, of which the most serious is multiple pregnancy. Extrapolating from these results, it is concluded that a well managed SIUI programme that selects patients appropriately, monitors them intensively and has in place effective strategies to manage over-responders safely, should be able to deliver at least a 15% live birth rate per cycle started with only a 5% cycle cancellation rate. Although SIUI birth rates are lower than IVF rates, the much lower cost of SIUI means that this treatment can be more cost-effective than IVF. However SIUI remains more risky than IVF and, despite careful management, high order multiple pregnancy rates will occasionally occur. It is estimated that the rate of unavoidable high order multiple pregnancies (triplets and above) is 4 per 1000 cycles started.

Two versus three embryos for transfer on day 3: influence of female age and embryo quality on outcome

Objective: The objective of this study was to determine the optimal number of embryos to transfer on day 3 in females up to age 38. The dual goals are to maintain a high pregnancy rate and minimize the multiple pregnancy rate. Design: This is a retrospective study with data collected from January 1999 through March 2003. All embryo transfers were performed on day 3 after oocyte retrieval and excluded any oocyte donor cases. Patients were classified by age into one of two groups: females <35, or females >35 and <38. Outcome comparisons (ongoing pregnancy rates defined as presence of a heart beat at 9 weeks gestation) were made by Chi-Square analysis. Only patients with at least 3 embryos at transfer were included in the data analysis. Materials and Methods: All patients underwent an ovarian stimulation protocol using either a GnRH agonist prior to stimulation with gonadotropins, or a GnRH antagonist following gonadotropin stimulation. Oocyte retrieval was performed 36 hrs post hCG administration and embryos were transferred approximately 72hrs post oocyte retrieval. Patients utilizing either standard IVF or ICSI were included in this study. Embryos were cultured in commercially prepared media and graded for quality (cell stage, degree of fragmentation, symmetry of blastomeres) immediately prior to transfer. The highest quality embryos available were chosen for transfer. Results: For the <35 age group, it was found that patients receiving 2 high quality embryos (lead embryo at least 8 cells and of the highest grade) at transfer (n=141) had an ongoing pregnancy rate of 55% while those receiving 3 such embryos (n=196) had an ongoing rate of 56% (P>.05). The singleton, twin and triplet rate for pregnancies of patients receiving 2 embryos was 62%, 38%, and 0%, respectively. Patients receiving 3 embryos had a singleton, twin, and triplet rate of 55%, 34 % and 11%, respectively. When the >35 and <38 age group was examined, it was found that the ongoing pregnancy rate of those patients receiving 3 embryos meeting the same criteria (lead embryo at least 8 cells of the highest grade) (n=123) was 53%. Those receiving 3 embryos had singleton, twin and triplet rates of 55%, 34%, and 8%, respectively (P>.05 when compared to <35 group). As there were no patients in this age group that electively chose only 2 embryos for transfer, these data cannot be directly compared to those of the <35 group receiving 2 embryos. Conclusion: These data raise an interesting possibility for the age group between 35 and 38. It is clear that in the under 35 age group, 3 embryos offer no advantage over 2 embryos when high quality embryos are available for transfer. Moreover, the addition of a third embryo in this group does not increase the overall pregnancy rate-only the high order multiple pregnancy rate (triplets). The fact that the 35–38 age group receiving 3 embryos displayed almost identical pregnancy rates as the under 35 group receiving 3 embryos and that the singleton, twin and triplet rates were not different between the groups suggests that even the older group may benefit from having only 2 high quality embryos transferred. These data suggests doing so would not compromise overall pregnancy rates but would have the benefit of reducing the high order multiple rates. Furthermore, these data fully support the SART guideline of transferring only 2 embryos in younger patients that have a good prognosis. In addition, these data suggest that extending that guideline to include patients up to 38 with a good prognosis may be justified.

Establishment and application of criteria for the elective transfer of two good-quality embryos to reduce high-order multiple pregnancies.

Aim : This study was carried out to establish criteria for the elective transfer of two good-quality embryos to reduce high-order multiple pregnancy rates. The pregnancy and multiple pregnancy rates per transfer were retrospectively analyzed in 128 in vitro fertilization and embryo transfer (IVF-ET) cycles. Results : The analysis revealed that the pregnancy and multiple pregnancy rates were 26.6% (34 of 128) and 23.5% (eight of 34), respectively. Five twin and three triplet pregnancies were included. The pregnancy rates in women 29years old and younger, 30-34years, 35-39years, and 40years and older were 21.2 (seven of 33), 37.0 (17 of 46), 25.8 (eight of 31), and 11.1% (two of 18), respectively. There was a significant difference of the pregnancy rates between 30 and 34-year-old and 40-year-old and older women (P<0.05). The multiple-pregnancy rate in women 40years and older was 0%. Three triplet pregnancies were established only in the first attempt of IVF-ET. The pregnancy rates in women, to whom good-quality embryos (0-4) were transferred, were 0% (none of 12) for 0, 17.2% (five of 29) for one, 41.2% (seven of 17) for two, 30.8% (12 of 39) for three, and 32.3% (10 of 31) for four and more embryos, respectively. The multiple pregnancy rates in women who had good-quality embryos of one, two, three, and four and more transferred were 0% (none of five), 23.5% (four of seven), 16.7% (two of 12), and 20.0% (two of 10), respectively. Conclusion : The criteria for the elective transfer of two good-quality embryos were established as follows: age<40years, a first treatment cycle, and more than three good-quality embryos available for transfer. After the application of the established criteria, the overall pregnancy and multiple pregnancy rates were 30.4% (14 of 46) and 14.3% (two of 14), respectively, which was satisfactory as compared with those in the 128 IVF-ET cycles before application of the criteria. An elective transfer of two good-quality embryos can be highly recommended to avoid high-order multiple pregnancies in subjects with the established criteria. (Reprod Med Biol 2002; 1: 23-29).

Blastocyst culture in human IVF: the final destination or a stop along the way?

In the field of human IVF, culturing embryos to the blastocyst stage has gained popularity within the past few years. The impetus to transfer blastocysts has been spurred by several factors: 1) the desire to improve implantation rates in infertility patients, 2) a desire to reduce the multiple pregnancy rate by transferring fewer embryos, 3) the desire to perform pre-implantation genetic diagnosis, and 4) the advent of sequential media. Although culturing human embryos to the blastocyst stage has improved implantation rates and reduced the incidence of multiple pregnancies in some patient populations, it has not worked for all populations of infertility patients. Factors that may affect the ability of a human embryo to reach the blastocyst stage include the patient's age, cohort of ova retrieved, the use of intracytoplasmic sperm injection of blastomere biopsy, culture conditions, or intrinsic factors within the embryo itself. Culture of human embryos to the blastocyst stage can be an effective method for improving implantation rates and reducing the high order multiple pregnancy rates seen in human IVF clinics when more than three embryos are transferred.

Development and Proven Efficacy of a Program-Specific Algorithm to Reduce High Order Multiple Pregnancy Rates

Objective: To develop an algorithm restricting the number of embryos to transfer on day 3 in order to minimize the incidence of high order multiple (HOM) pregnancies [i.e. more than 2 fetal hearts (FHs)], while maximizing pregnancy rates.

Can High-Order Multiple Pregnancy Rates Be Reduced in Infertility Treatment?

Dramatic successes in infertility therapy have unfortunately yielded increased high-order multiple pregnancies. To determine whether the incidence of high-order multiple pregnancies could be reduced without decreasing pregnancy rates, these clinicians analyzed data from 3347 consecutive treatment cycles in 1494 infertile women treated with gonadotropin to …