Triplet Rate Research Articles

To pay or not to pay

Over the past two decades, IVF has helped hundreds of thousands of infertile couples around the world become parents. Despite its growing success and widespread use in the United States to treat infertility, IVF remains primarily a privately funded treatment. Most health plans exclude it from coverage on the grounds that it is not medically necessary. In contrast, other developed countries (such as Australia, Austria, Denmark, Finland, France, Germany, Iceland, The Netherlands, Norway, and Sweden) have made provisions in their national health policies to cover infertility treatment, including IVF (1). In the United States in 2001, the median cost per IVF cycle was estimated to be $9,226 (2). Because of this high out-of-pocket cost, many financially constrained infertile couples are excluded from access to this care.

A simple solution to reducing multiple pregnancy rates: utilizing age as the predominant factor

Background: According to the Educational Bulletin published by American Society for Reproductive Medicine, November 2000 issue, multiple pregnancies have increased over the past 15 years. 40% of these pregnancies were attributable to ovulation induction drugs without assisted reproductive technologies (ART), and 40% were attributable to ART. Objective: We reviewed our multiple gestation rates after the implementation of the policy of ≤2 embryos would be transferred in women <35 yr. in a fresh IVF cycle. In this age group with a previous history of failed IVF were assessed on a case-by-case basis and did not necessarily fall into this category. Materials and Methods: A retrospective analysis of multiple pregnancy rates for the years 2000 and 2001 was performed. ART cycles for 2000 and 2001 were included in the analysis and subgroup analysis was performed on IVF only (all and <35 years), as well as ART (all and <35 years). Statistical analysis was performed by chi-square analysis. Results: All triplet rates except for ART procedures performed on women <35, were significantly reduced without a negative impact on pregnancy rates and without performing selective fetal reductions in the year 2001. Conclusion: Since the implementation of this policy, this clinic has experienced a significant reduction in multiple pregnancies. The results of this retrospective analysis suggest the possibility that this policy of limiting the number of embryos transferred in young women could also be extended to other types of ART cycles. Based on these results, we have implemented this policy in our frozen embryo transfer (FET) and donor egg cycles without jeopardizing our pregnancy rates. Table 1 Table 1Ongoing pregnancy rates for 2000 & 2001.GroupsSingletonsTwinsTriplets∗P values (Power)2000 (%)2001 (%)2000 (%)2001 (%)2000 (%)2001 (%)ART257/420 (61.2)259/387 (66.9)137/420 (32.6)118/387 (30.5)26/420 (6.2)∗10/387 (2.6)∗0.021 (0.635)ART (<35)137/232 (59.1)133/206 (64.6)80/232 (34.5)67/206 (32.5)15/232 (7.8)6/206 (2.9)IVF186/327 (56.9)186/289 (64.4)116/327 (35.5)95/289 (32.9)25/327 (7.6)∗8/289 (2.8)∗0.012 (0.713)IVF (<35)105/193 (54.4)109/170 (64.1)73/193 (37.8)57/170 (33.5)15/193 (7.8)∗4/170 (2.4)∗0.038 (0.538) Open table in a new tab

Influence of Negatively Charged Interfaces on the Ground and Excited State Properties of Methylene Blue¶

Properties of the ground and excited states of methylene blue (MB) were studied in negatively charged vesicles, normal and reverse micelles and sodium chloride solutions. All these systems induce dimer formation as attested by the appearance of the dimer band in the absorption spectra (lamdaD approximately 600 nm). In reverse micelles the dimerization constant (KD) corrected for the aqueous pseudophase volume fraction is two-three orders of magnitude smaller than KD of MB in water, and it does not change when W0 is increased from 0.5 to 10. Differences in the fluorescence intensity as a function of dimer-monomer ratio as well as in the resonance light scattering spectra indicate that distinct types of dimers are induced in sodium dodecyl sulfate (SDS) micelles and aerosol-OT (sodium dioctyl sulfoxinate, AOT) reversed micelles. The properties of the photoinduced transient species of MB in these systems were studied by time-resolved near infrared (NIR) emission (efficiency of singlet oxygen generation), by laser flash photolysis (transient spectra, yield and decay rate of triplets) and by thermal lensing (amount of heat deposited in the medium). The competition between electron transfer (dye*-dye) and energy transfer (dye*-O2) reactions was accessed as a function of the dimer-monomer ratio. The lower yield of electron transfer observed for dimers in AOT reverse micelles and intact vesicles compared with SDS micelles and frozen vesicles at similar dimer-monomer ratios is related with the different types of aggregates induced by each interface.

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.

Neonatal Outcome in Pregnancies From Ovarian Stimulation

In Brief OBJECTIVE To study the neonatal outcome in pregnancies after ovarian stimulation, not including in vitro fertilization. The outcomes studied were multiple birth, preterm birth, and low birth weight among singletons, congenital malformations, and infant death. METHODS We identified 4029 women who delivered between 1995–1999 after ovarian stimulation alone and compared them with 438,582 women who neither had ovarian stimulation nor in vitro fertilization. We controlled for the confounding effect of year of birth, maternal age, parity, and length of subfertility before the pregnancy. RESULTS The twinning rate was 5.9% in the study group and 1.2% in the control group. The triplet rate was 0.5% in the study group and 0.02% in the control group. A nearly doubling of the rate of monozygotic twinning was indicated in the study group compared with the control group. There was an excess of singleton preterm births and low birth weight infants in the study group, but this was mainly explainable by confounding of maternal age, parity, and subfertility. The rates of congenital malformations and perinatal deaths were increased, also mainly explainable by maternal characteristics. No increase in specific types of congenital malformations was seen. CONCLUSION As the deviations in neonatal outcome after ovarian stimulation alone were reduced or disappeared when the confounding of maternal age, parity, and subfertility was taken into consideration, there is probably little direct effect of the stimulation procedure as such. Suboptimum neonatal outcome after ovarian stimulation, including an increased risk for congenital malformations, is apparently mainly an effect of maternal characteristics related to subfertility.

Neonatal outcome in pregnancies from ovarian stimulation

OBJECTIVE: To study the neonatal outcome in pregnancies after ovarian stimulation, not including in vitro fertilization. The outcomes studied were multiple birth, preterm birth, and low birth weight among singletons, congenital malformations, and infant death. METHODS: We identified 4029 women who delivered between 1995–1999 after ovarian stimulation alone and compared them with 438,582 women who neither had ovarian stimulation nor in vitro fertilization. We controlled for the confounding effect of year of birth, maternal age, parity, and length of subfertility before the pregnancy. RESULTS: The twinning rate was 5.9% in the study group and 1.2% in the control group. The triplet rate was 0.5% in the study group and 0.02% in the control group. A nearly doubling of the rate of monozygotic twinning was indicated in the study group compared with the control group. There was an excess of singleton preterm births and low birth weight infants in the study group, but this was mainly explainable by confounding of maternal age, parity, and subfertility. The rates of congenital malformations and perinatal deaths were increased, also mainly explainable by maternal characteristics. No increase in specific types of congenital malformations was seen. CONCLUSION: As the deviations in neonatal outcome after ovarian stimulation alone were reduced or disappeared when the confounding of maternal age, parity, and subfertility was taken into consideration, there is probably little direct effect of the stimulation procedure as such.

Trends in the occurrence, determinants, and consequences of multiple births

After a substantial decrease in the middle of the 20th century, multiple pregnancy rates have increased in many Western countries. Between the mid-1970s and 1998, the rate of twin pregnancies increased by 50% to 60% in England and Wales, France, and the United States. The rates of triplet or higher-order multiple pregnancies increased by 310% in France, 430% in England and Wales, and 696% in the United States. One fourth to one third of the increase in twin or triplet pregnancies are attributable to a contemporaneous increase in maternal age. Furthermore, in countries with high occurrence of multiple births, 30% to 50% of twin pregnancies and at least 75% of triplet pregnancies occur after infertility treatment. The impact of the increase in multiple births on preterm delivery rates in the overall population is mainly attributable to twin pregnancies. In Canada, France, and the United States, an increase in preterm births among multiples contributed almost as much as the increase in occurrence of multiple births to the increase or stabilization of the overall rates of preterm delivery observed in these countries.

The influence of the photophysics of 2-substituted thioxanthones on their activity as photoinitiators

The polymerization of methyl methacrylate photoinitiated by thioxanthones (TXs) substituted in the position 2 of the chromophore ring in the presence of 2-( N, N-diethylamino)ethanol has been investigated. The photoinitiation efficiency of these systems is highly dependent on the structure of the 2-substituent. At high amine concentrations, compounds with electron-withdrawing substituents appear as more efficient photoinitiators. The photophysics of the ketones was studied in the polymerization medium. These data show that the singlet excited state of TXs is deactivated by the amine with a rate constant near the diffusional control limit. The triplet rate constants for quenching by the amine and the monomer are highly dependent on the ketone structure. Compounds with electron-withdrawing substituents in the position 2 are more reactive. These studies allow to simulate the dependence of the photoinitiation efficiency with the amine concentration and indicate that the active radicals are produced by the interaction of the ketone triplet with the amine.

High rates of embryonic loss, yet high incidence of multiple births in human art: is this paradoxical?

Humans have low natural fecundity, as the probability of establishing a viable conception in any one menstrual cycle is 20–25% for a healthy, fertile couple. There are numerous underlying causes for this low rate of human fertility, not the least of which are intrinsic abnormalities within the oocyte and/or embryo, which likely account for greater than 50% of failed conceptions. During assisted reproduction technology (ART) interventions, controlled ovarian stimulation is used to obtain several oocytes in attempts to increase the likelihood of having at least one developmentally competent embryo available for transfer. However, current techniques for identifying the competent embryo(s) are by no means perfect. These limitations, coupled with pressures to maximize the chance of pregnancy, typically result in the transfer of multiple embryos. Not surprisingly, this practice has resulted in an unacceptably high rate of multiple pregnancies arising from ART. During the last few years, concerted efforts have focused on reducing these rates. Programs for ART are developing patient-specific policies, restricting the number of embryos to transfer. In addition, strategies are being adopted to improve the accuracy for selecting viable embryos for transfer. One such strategy involves further refinement of morphological criteria associated with improved viability by considering, for example, pronuclei disposition, nucleolar organization, and identification of the fast-cleaving embryos with only mononucleate blastomeres. Another strategy employs pre-implantation genetic diagnosis (PGD) whereby a biopsied blastomere is tested for ploidy using fluorescence in situ hybridization (FISH). A final strategy involves extending the duration of culture to the blastocyst stage, thereby allowing self-selection of those embryos capable of proceeding to blastulation and exclusion of those less viable embryos that succumb to developmental arrest. Together, these strategies are enabling fewer embryos of higher quality to be transferred. Accordingly, the overall pregnancy rate from ART continues to increase, while the rate of triplet and higher order multiple births continues to decline. Nevertheless, the high incidence of intrinsic developmental anomalies in human oocytes inevitably will continue to result in a high degree of embryonic loss in ART.

Twinning rate in a sample from a Brazilian hospital with a high standard of reproductive care.

Epidemiological studies on twin births have been motivated mostly by the positive correlation between twinning rate and human fertility, prematurity, low birth weight, increased risk of infant death and long term risk for morbidity. This paper intends to estimate the incidence of multiple births in a private hospital in Brazil with a high standard of reproductive care, and to evaluate the effects of maternal age, gestation order and assisted fertilization on twinning rate. Retrospective analysis. First-class tertiary private hospital, São Paulo, Brazil. The multiple birth rate was investigated among 7,997 deliveries from 1995 to 1998, including 7,786 singletons, 193 twins, 17 triplets and one quadruplet. The rates per 1,000 dizygotic and monozygotic pairs and for triplets were estimated as 19.51, 4.50 and 2.13, respectively. The dizygotic and triplet rates were the highest observed in Brazil up to the present day. The twinning rate among primigravidae older than 30 years was very high (45.02 per 1,000) and was due to a disproportionately high frequency of dizygotic pairs. The triplet rate was also very high among the mothers of this age group (5.71 per 1,000). These facts are strong indicators that these women were the ones most frequently submitted to assisted reproductive techniques. The mean maternal age of the studied population was about six years higher than that estimated for mothers in the general population of southeastern Brazil. Primigravidae aged under 30 years as well as multigravidae showed similar twinning rates, which were almost 20 per 1,000. Among the deliveries of multigravidae older than 30 years, an unusually high frequency of monozygotic twins was observed (7.04 per 1,000), probably as a consequence of the residual effect of long-term use of oral contraceptives. The dizygotic twinning rate increased from 13.51 to 28.98 per 1,000 over the four years studied, with the twinning rate for primigravidae over 30 years old in 1998 being twice that observed in 1995. The mean maternal age was also high during this period, but the extremely high increase in twinning rate observed cannot be attributed solely to this variable. Assisted fertilization seems to be the most probable cause of this unusually high twinning rate.

Estimated number of multiplets under 16 years using two sets of census data in Japan: 1990 and 1995.

Data for sets of multiples under 16 years of age were obtained from the population censuses of Japan in 1990 and 1995. These numbered 147,188 twin pairs, 1410 sets of triplets, 59 sets of quadruplets, and 3 sets of quintuplets in 1990, with the corresponding numbers in 1995 being 141,354, 2,211, 136 and 12, respectively. The total number of sets of multiples was 148,660 in 1990 and 143,713 in 1995. Twinning, triplet, quadruplet and quintuplet rates were estimated for each age. Rates of monozygotic twins and triplets remained constant age by age up to 15 years, while the dizygotic twinning rate, and rates of di- and tri-zygotic triplets decreased over the same period. Quadruplet and quintuplet rates also decreased. The accuracy of estimating number of multiples from census data is discussed using data on vital statistics.

Estimated Number of Multiplets Under 16 Years Using Two Sets of Census Data in Japan: 1990 and 1995

AbstractData for sets of multiples under 16 years of age were obtained from the population censuses of Japan in 1990 and 1995. These numbered 147,188 twin pairs, 1410 sets of triplets, 59 sets of quadruplets, and 3 sets of quintuplets in 1990, with the corresponding numbers in 1995 being 141,354, 2,211, 136 and 12, respectively. The total number of sets of multiples was 148,660 in 1990 and 143,713 in 1995. Twinning, triplet, quadruplet and quintuplet rates were estimated for each age. Rates of monozygotic twins and triplets remained constant age by age up to 15 years, while the dizygotic twinning rate, and rates of di- and tri-zygotic triplets decreased over the same period. Quadruplet and quintuplet rates also decreased. The accuracy of estimating number of multiples from census data is discussed using data on vital statistics.

Epidemiological trends in multiple births in the United States, 1971-1998.

The astounding rise in multiple births in the United States continues. We analyzed live birth files from the U.S. National Center for Health Statistics. Twin, triplet, quadruplet, and quintuplet+ rates were calculated for the period 1971-1977 and for each year between 1990 and 1998. Triplet rates were also computed within categories of mother's education and age. The twin rate increased from 1.8% in 1971-77 to 2.8% in 1998. The rate of triplets increased 5.9-fold, quadruplets 11.9-fold, and quintuplets+ 5.3-fold between 1971-77 and 1998. Increases in triplet rates were much more marked among births to university-educated women and women 30 years and older. Among women 45 years and older, the triplet rate was approximately fifty times higher in 1998 than in 1971-77. This group of older women (> or = 45 years) had the highest multiple birth rate in 1998.

Epidemiological trends in multiple births in the United States, 1971–1998

AbstractThe astounding rise in multiple births in the United States continues. We analyzed live birth files from the U.S. National Center for Health Statistics. Twin, triplet, quadruplet, and quintuplet+ rates were calculated for the period 1971–1977 and for each year between 1990 and 1998. Triplet rates were also computed within categories of mother's education and age. The twin rate increased from 1.8% in 1971–77 to 2.8% in 1998. The rate of triplets increased 5.9-fold, quadruplets 11.9-fold, and quintuplets+ 5.3-fold between 1971–77 and 1998. Increases in triplet rates were much more marked among births to university-educated women and women 30 years and older. Among women 45 years and older, the triplet rate was approximately fifty times higher in 1998 than in 1971–77. This group of older women (≥ 45 years) had the highest multiple birth rate in 1998.

Multiple gestations in assisted reproductive technology: Can they be avoided with blastocyst transfers?

Objective: Blastocysts are advanced-stage embryos with high implantation potential; theoretically, limited numbers of blastocysts can be used for embryo transfer to achieve good pregnancy rates with low multiple pregnancy rates. Clinical outcomes of a newly implemented blastocyst transfer program were evaluated. Study Design: This study is a retrospective analysis of 553 blastocyst transfer cycles performed by a university-based in vitro fertilization program; risk factors associated with multiple gestations were analyzed. Results: An average of 2.2 embryos were used for embryo transfer. The overall clinical pregnancy rate per embryo transfer was 45.1%; multiple gestation, twin, and triplet rates were 40.9%, 36.5%, and 4.3%, respectively. Multiple gestations increased significantly (1) when embryo transfer was done on day 5, (2) when ≥2 blastocysts were present on day 5, and (3) when maternal age was ≤30 years. Conclusion: In spite of a conservative approach to the number of blastocysts used for embryo transfer, the overall multiple pregnancy rate was high, and triplet pregnancies did occur. (Am J Obstet Gynecol 2001;184:1471-7.)

Monozygotic twinning after assisted reproductive techniques: a phenomenon independent of micromanipulation

A 3 year retrospective analysis was conducted of pregnancies achieved after various assisted reproductive treatment modalities in our infertility practice, to calculate and compare the rates of monozygotic twinning (MZT). A total of 731 pregnancies achieved after various assisted reproduction treatments were reviewed. Gonadotrophin therapy for induction of ovulation and controlled ovarian hyperstimulation (COH) yielded 129 clinical pregnancies. Conventional IVF yielded 139 pregnancies. IVF and intracytoplasmic sperm injection (ICSI) with or without assisted hatching (AH) yielded 463 pregnancies, all during the same time period. The rates of multiple pregnancy (monozygotic and dizygotic) twins and triplets were recorded. MZT was found in 1.5% of ovulation induction or COH pregnancies (2/129). The incidence of MZT after conventional IVF was 0.72% (1/139). After IVF-ICSI/AH, MZT was found in 0.86% (4/463). The overall rate of MZT was 0.95% (7/731). Five cases were dizygotic triplets and two cases were monozygotic twins. We found the rate of MZT after assisted reproduction treatment increased more than two-fold over the background rate in the general population. Dizygotic triplets were found more often than monozygotic twins. The rate of MZT was consistently increased, irrespective of treatment modality or micromanipulation. This may signify that the aetiology of increased MZT after assisted reproduction is the gonadotrophin treatment rather than in-vitro conditions, micromanipulation, or multiple embryo transfer.

Alternative embryo transfer on day 3 or day 5 for reducing the risk of multiple gestations.

This study was carried out to reduce the possibility of high-order multiple gestations and the failure of embryo transfer by determining their replacement date based on the number and quality of 2-day embryos. All zygotes were cocultured with cumulus cells in 10 microliters of YS medium containing 10% human follicular fluid (hFF) for 48 or 96 hr. In period I, all embryos were transferred on day 3 (1032 cycles). In period II, the embryos were transferred on either day 3 or day 5 by determining their replacement date based on the number and quality of 2-day embryos: there were 2701 patients in whom embryos were replaced on day 3 (in the case that the number of zygotes was less than eight and the number of good-quality embryos was less than three) and 1952 patients less than 40 years old in whom embryos were replaced on day 5 (in the case that the number of zygotes was eight or more and/or the number of good-quality embryos was three or more). On the other hand, patients who were 40 years old or more were alloted to day 3 transfer cycles, regardless of the number and quality of the 2-day embryos, due to the possibility of their not producing blastocyst-stage embryos in vitro. The number of embryos transferred in period II was 2.9 +/- 0.6, while that in period I was 3.7 +/- 0.5. The multiple pregnancy rate was significantly decreased in period II (30.7%) compared to that (49.6%) in period I, while the pregnancy and implantation rates in period II (36.1 and 16.4%, respectively) were not lower than those (34.9 and 16.1%, respectively) in period I. The rate of triplet or more gestations was significantly minimized in period II (2.3%) compared to that in period I (26.5%). We propose that determination of the date on which embryos should be transferred based on the number and quality of embryos on day 2 may help to maintain an acceptable pregnancy rate, while minimizing embryo transfer failure and high-order multiple gestations.

How to avoid multiple pregnancies in assistive reproductive technologies.

Since 1980, there has been a worldwide dramatic increase in multiple births. This seems to be due to an increase in the age of reproduction, the use of ovulation induction, and the use of in vitro fertilization. Scarce data suggest that each of these causes is responsible for about one-third of the problem, although quintuplets and more are almost invariably due to ovulation induction. There has been little or no effort to issue guidelines or regulations with respect to ovulation induction, but there has been much advice as to how to control the problem in in vitro fertilization by limiting the number of embryos to be transferred. In sum, a good selection of high-quality embryos on day 3 would allow a high rate of pregnancy with the transfer of one or two blastocysts. Good results of cryopreservation must be part of an agreement in an in vitro fertilization program. If singleton live birthrates were considered to be the principal outcome of assisted reproductive technologies reported by centers and registry, twin and triplet rates should also be reported separately. And finally, if financial considerations would not limit the cost of reimbursement to in vitro fertilization procedures, the number of procedures could be increased with fewer embryos transferred.

Three Years Experience Transferring Two Day 3 Embryos in Select Patients to Reduce Triplets

Objective: To reduce the higher order multiple pregnancy rates by replacing two day 3 embryos in good prognosis patients at risk for multiple pregnancy. Design: Clinical pregnancy, implantation and multiple pregnancy rates are presented. Materials and Methods: In 1997, patients in our clinic who were considered at risk for multiple pregnancy were those ≤34 years old who had good ovarian stimulation and good embryo quality with some frozen. In 1998 and 1999, this category was expanded to include those patients ≤36 years old. In these good prognosis patients, two embryos were transferred on day 3. Results: legendlegendPR–pregnancy rate, IR–implantation rate/embryo, and MPR–multiple pregnancy rate.No. ET’s/ total (%)Clinical PR %IR %MPR %Twin %Triplet %1997114/38062.346.547.946.51.4(30.0)(71/114)(106/228)(34/71)(33/71)(1/71)1998191/43562.846.145.845.00.8(43.9)(120/191)(176/382)(55/120)(54/120)(1/120)1999228/49162.342.333.130.32.8(46.4)(142/228)(193/456)(47/142)(43/142)(4/142)legend PR–pregnancy rate, IR–implantation rate/embryo, and MPR–multiple pregnancy rate. Open table in a new tab By way of comparison, in 1996 the minimum number of embryos transferred was three when available. The PR in a similar group of good prognosis patients was 63.4%, IR was 40.3% and the triplet rate was 15.7%. Conclusion: Selecting good prognosis patients at risk for multiple pregnancy and reducing the number of day 3 embryos transferred to two will help to reduce the risk of higher order multiple pregnancies and not compromise pregnancy outcomes.

Chemically induced dynamic electron polarization investigation of the triplet‐radical system in the solution of the triplet quencher

AbstractThe chemically induced dynamic electron polarization (CIDEP) of the triplet molecule/triplet quencher/2, 2, 6, 6‐tetramethyl‐1‐piperidinyloxyl (TEMPO) systems were measured using the high time‐resolved ESR spectrometer. The competition between the radical‐triplet pair mechanism (RTPM) and triplet mechanism (TM) or radical pair mechanism (KIM) polarization in the solution of the triplet quencher was investigated, and the relationships between reaction rate of the radical‐triplet pair and quenching rate of triplet was deduced.