Incidence Of Monozygotic Twinning Research Articles

Does Co-Culture Avoid Monozygotic Twinning? A Case-Control Study

Multiple pregnancy rate has risen dramatically during the last decade, basically due to the widespread use of assisted reproductive techniques (ART). Apart from the multiple pregnancy rate, a special consideration should be given to the increasing rate of monozygotic twinning (MZT). Blastocyst transfer has been proposed as a cause of monozygotic pregnancies. The aim of our study was to compare the incidence of MZT in a large series of patients undergoing embryo transferences at blastocyst stage, using co-culture or sequential media.

Does the Incidence of Monozygotic Twinning With Blastocyst Transfer Decrease Over Time?

The main advantage of blastocyst transfer (BT) is its high implantation rate, which encourages the transfer of fewer embryos and may facilitate the reduction of fraternal multiple births. However, this benefit is potentially offset by the increased incidence of monozygotic twins (MZT) described by several reports in the literature. A review of these reports shows that some of them note a disproportionately higher incidence of MZT in the early stages of BT implementation for a particular program.

Visualization of atypical hatching of a human blastocyst in vitro forming two identical embryos

A significant increase in the incidence of monozygotic twinning has been reported after embryo transfer at the blastocyst stage compared with day 2– or day 3–stage embryos (1, 2). There is much speculation as to why this happens. We report a case of a human blastocyst dividing into two complete halves after atypical hatching in vitro, which may be a possible mechanism of monozygotic twinning.

Case report: visualization of atypical hatching of a human blastocyst in vitro forming a monozygotic twin

Objective: A significant increase in the incidence of monozygotic twinning (MZT) has been reported after embryo transfer at the blastocyst stage compared to day 2–3 stage embryos. However, there is much speculation as to why this happens. We report here a case of a human blastocyst dividing into two complete halves after atypical hatching in vitro which may demonstrate a possible mechanism of a MZT pregnancy.

Monozygotic twinning: a significant risk when performing blastocyst transfer as compared to day three embryo transfer

Objective: Blastocyst transfer has been associated with an increased risk of resultant monozygotic twinning. We sought to evaluate the risks of monozygotic twinning in blastocyst transfers as compared to day three embryo transfer in a large cohort of IVF patients. We also sought to compare the risk of monozygotic twinning in fresh and frozen/ thawed blastocyst transfer. Design: Retrospective analysis of IVF outcome for 5614 consecutive IVF fresh cycles and 157 frozen/thawed blastocyst transfers. Materials and Methods: We analyzed 5614 consecutive fresh IVF cycles for the risk of monozygotic twinning in both day three and day five embryo transfers. We also compared a group of 157 frozen/ thawed blastocyst transfers. The study time frame was from July 2000 to March 2003. All patients with a fresh IVF cycle undergoing a transfer were included in the study. The choice of elective blastocyst transfer was determined by the following criteria: the number of oocytes harvested, the number of resultant fertilized embryos, quality of embryos on day three and past IVF history. Incidence of monozygotic twinning was compared between day three and day five embryo transfers. Statistics included Chi-square and Student’s t-test where appropriate. P value < 0.05 was considered significant. Results: Five-thousand six hundred and fourteen consecutive IVF cycles were analyzed. 5197 patients underwent a day three embryo transfer resulting a clinical pregnancy rate of 44.3% (2302/5197). Four hundred and seventeen patients underwent a fresh day five embryo transfer resulting in a clinical pregnancy rate of 69.3% (289/417). Monozygotic twinning was almost eightfold increased when comparing day five to day three embryo transfers (see Table). A lower number of oocytes harvested and a lower number of embryos available for embryo transfer were strongly predictive of monozygotic twinning in day three embryo transfers (11.6 ± 5.3 vs. 7.8 ± 4.8 oocytes, day 3 non-monozygotic twinning vs. day 3 monozygotic twinning; P = 0.01; and 3.5 ± 1.0 vs. 2.0 ± 0.8 embryos transferred, day 3 non-monozygotic twinning vs. day 3 monozygotic twinning; P < 0.001). No factors were found to be predictive of day 5 monozygotic pregnancies. Frozen blastocyst transfers were equally likely to result in monozygotic twinning as compared to a fresh day five embryo transfer (2/99 vs. 11/289; P = NS). Tabled 1 Conclusion: In this very large cohort of patients we have demonstrated a nearly eightfold increase in monozygotic twinning when comparing day five to day three embryo transfers. Patients need to be counseled in regards to this finding prior to undergoing a day five embryo transfer. A lowered selection of embryos for replacement appears to be predictive of day three monozygotic twinning.

Culture conditions and not prolonged culture time are responsible for monozygotic twinning in human in vitro fertilization

Culture conditions and not prolonged culture time are responsible for monozygotic twinning in human in vitro fertilization

Incidence of monozygotic twinning with blastocyst transfer compared to cleavage-stage transfer

Objective To evaluate the incidence of monozygotic twinning (MZT) in pregnancies conceived after blastocyst transfer compared to cleavage-stage transfer. Design Retrospective study. Setting University IVF program. Patient(s) All IVF patients with viable pregnancies conceived during a 4-year period. Intervention(s) Blastocyst transfer or day 3 ET. Main outcome measure(s) Incidence of MZT assessed by transvaginal ultrasound. Result(s) There were 11 incidences of MZT in 197 viable pregnancies (5.6%) with blastocyst transfer compared to 7 of 357 viable pregnancies (2%) with day 3 ET. In 10 of 18 pregnancies, MZT was observed in the setting of a higher order multiple gestation (6 of 11 for blastocyst transfer and 4 of 7 for day 3 ET). In the day 3 ET group, assisted hatching or intracytoplasmic sperm injection (ICSI) did not increase MZT (4 of 213, 1.9%) compared to cycles without zona breaching (3 of 144, 2.1%). Similarly, in the blastocyst-transfer group, ICSI did not increase the incidence of MZT (4 of 74, 5.5% for ICSI and 7 of 123, 5.7% for non-ICSI IVF). Conclusion(s) Compared to day 3 ET, blastocyst transfer appears to significantly increase the incidence of gestations with MZT. This information should be taken into account when counseling patients about the pros and cons of extended culture.

Incidence of monozygotic twinning with blastocyst transfer compared to cleavage stage transfer

Objective: A higher incidence of monozygotic twinning (MZT) has been reported with IVF especially when the zona pellucida is breached. A few reports have suggested that blastocyst transfer(BT) may further predispose to MZT but information specifically comparing blastocyst to cleavage stage transfer, with respect to the incidence of MZT, is lacking. The present study addresses this issue in a large series of day 3 and day 5 embryo transfers(ET) performed during the same time period.Design: Retrospective study.Materials/Methods: All viable pregnancies conceived in our IVF program since January 1998 were analyzed. Embryos were cultured in P1 + 10%SSS (Irvine Scientific) until day 3 and moved to Blastocyst Medium + 10%SSS (Irvine Scientific) if extended culture was performed. Viable pregnancies were initially assessed by vaginal ultrasound at 7 weeks of gestation and the final outcome of each pregnancy was recorded. The incidence of MZT was examined for day 3 and day 5 transfers.Results: There were 11 incidences of MZT out of 197 viable pregnancies (5.6%) with BT compared to 7 out of 357 viable pregnancies (2%) with day 3 ET (p <0.03). Interestingly, in 10 out of 18 pregnancies, MZT was observed in the setting of a high-order multiple gestation (6/11 for BT and 3/7 for day 3-ET). In the day 3-ET group, assisted hatching and/or ICSI did not increase MZT (4/213 =1.9%) compared to cycles without zona breaching (3/144=2.1%). Similarly, in the BT group, ICSI did not increase the incidence of MZT (4/74 =5.5% for ICSI and 7/123=5.7% for non-ICSI IVF). In the BT group, the final outcome of the pregnancies showed spontaneous resolution of one of the MZ twins in 4/11 cases and one spontaneous loss of the entire pregnancy, while in 6/11 cases MZT persisted (one triplet pregnancy had multifetal reduction of the MZ twins). In the day 3-ET group, MZT persisted in all 7 pregnancies (4 had multifetal reduction).Conclusions: Compared to day 3-ET, BT seems to significantly increase the incidence of gestations with MZT. This information should be taken into account when counseling patients about the pros and cons of extended culture. The mechanism of MZT is likely to be multifactorial. It could be related to blastocyst hatching from a zona which has been hardened by prolonged culture, combined with altered polarity and decreased adhesiveness of the inner cell mass as well as increased apoptosis in media containing excessive glucose levels.Supported by: None Objective: A higher incidence of monozygotic twinning (MZT) has been reported with IVF especially when the zona pellucida is breached. A few reports have suggested that blastocyst transfer(BT) may further predispose to MZT but information specifically comparing blastocyst to cleavage stage transfer, with respect to the incidence of MZT, is lacking. The present study addresses this issue in a large series of day 3 and day 5 embryo transfers(ET) performed during the same time period. Design: Retrospective study. Materials/Methods: All viable pregnancies conceived in our IVF program since January 1998 were analyzed. Embryos were cultured in P1 + 10%SSS (Irvine Scientific) until day 3 and moved to Blastocyst Medium + 10%SSS (Irvine Scientific) if extended culture was performed. Viable pregnancies were initially assessed by vaginal ultrasound at 7 weeks of gestation and the final outcome of each pregnancy was recorded. The incidence of MZT was examined for day 3 and day 5 transfers. Results: There were 11 incidences of MZT out of 197 viable pregnancies (5.6%) with BT compared to 7 out of 357 viable pregnancies (2%) with day 3 ET (p <0.03). Interestingly, in 10 out of 18 pregnancies, MZT was observed in the setting of a high-order multiple gestation (6/11 for BT and 3/7 for day 3-ET). In the day 3-ET group, assisted hatching and/or ICSI did not increase MZT (4/213 =1.9%) compared to cycles without zona breaching (3/144=2.1%). Similarly, in the BT group, ICSI did not increase the incidence of MZT (4/74 =5.5% for ICSI and 7/123=5.7% for non-ICSI IVF). In the BT group, the final outcome of the pregnancies showed spontaneous resolution of one of the MZ twins in 4/11 cases and one spontaneous loss of the entire pregnancy, while in 6/11 cases MZT persisted (one triplet pregnancy had multifetal reduction of the MZ twins). In the day 3-ET group, MZT persisted in all 7 pregnancies (4 had multifetal reduction). Conclusions: Compared to day 3-ET, BT seems to significantly increase the incidence of gestations with MZT. This information should be taken into account when counseling patients about the pros and cons of extended culture. The mechanism of MZT is likely to be multifactorial. It could be related to blastocyst hatching from a zona which has been hardened by prolonged culture, combined with altered polarity and decreased adhesiveness of the inner cell mass as well as increased apoptosis in media containing excessive glucose levels. Supported by: None

The origin of monozygotic twinning

The incidence of monozygotic twinning appears to be increasing within the field of assisted human reproduction. Many theories have been put forward as to how and when this occurs. Whatever the cause, the normal events of embryo development, which necessarily involve axis formation, patterning and polarization, need to be adhered to in order to obtain a viable offspring. This paper describes the course of development in terms of axis formation and polarity and offers suggestions as to how either a disruption of this or duplication events in the course of the formation of these parameters could prevent or contribute to a twinning event. The likelihood of twinning occurring at any point is discussed in terms of the establishment of polarity and axes.

Thoughts and observations on patterning in early mammalian development

The preimplantation mammalian conceptus shows an impressive ability to develop normally following the loss, gain or rearrangement of cells. This has prompted the view that, unlike in other species, patterning in mammals cannot depend on information that is already present in the zygote before it begins to cleave. However, various findings are hard to reconcile with this conclusion, including evidence that the incidence of monozygotic twinning is sensitive to the conditions to which eggs or very early concepti are exposed. Possible causes of early twinning are discussed, and it is argued that partial hatching of the conceptus through a hernia in the zona pellucida cannot account for all cases. Moreover, it remains questionable whether studies on aggregated morulae and isolated blastomeres really provide compelling evidence against the existence of indispensible patterning information in the egg. Finally, regularities in axial relationships between the blastocyst and zygote have been revealed employing strictly non-invasive techniques. These show that, at least in normal development, patterning begins before cleavage.

Increase in the monozygotic twinning rate after intracytoplasmic sperm injection and blastocyst stage embryo transfer

Increase in the monozygotic twinning rate after intracytoplasmic sperm injection and blastocyst stage embryo transfer

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.

Monozygotic twins and transfer at the blastocyst stage after ICSI

The incidence of monozygotic twinning (MZT) is higher in pregnancies conceived after assisted reproduction than after natural conception. Alterations, produced by ovarian stimulation, in-vitro culture conditions and specifically alterations of zona pellucida are mentioned as possible causes of this phenomenon. A retrospective review was performed of the incidence of MZT in pregnancies generated in our centre during the period of January 1996 to December 1999. This variable was compared in 129 gestations that resulted from blastocyst transfer (occurring from September 1998 to August 1999) with 814 pregnancies produced by transfers of 4- to 8-cell embryos. Follicular development was induced with human menopausal gonadotrophin and urinary FSH during 1996 and 1997 and with recombinant FSH during 1998 and 1999. Blastocysts were cultured in sequential media using S1 or G1 up to 72 h and S2 or G2 to day 5. Five of the 129 pregnancies generated by blastocyst transfers were complicated by MZT gestation (3.9%). In comparison, only six of 814 pregnancies occurred from 4- to 8-cell transfers (0.7%), a difference that is statistically significant (P< 0.001 with Yates correction). The results confirm an increase of MZT in pregnancies from intracytoplasmic sperm injection as compared to the natural incidence. Moreover, the frequency of MZT was significantly higher when transfers were performed at the blastocyst stage, suggesting that extended in-vitro culture of embryos may be associated with alterations of the zona pellucida and the hatching process.

High constant incidence in twins and other relatives of women with breast cancer.

The incidence of breast cancer rises steeply between ages 25 and 50, and more slowly thereafter. In contrast, the incidence in the unaffected (contralateral) breast of women who have had breast cancer remains constant at about 0.7% per year for at least the next 20 years after diagnosis, irrespective of age at first diagnosis. The incidence in relatives of the patients seems to show a similar pattern. The incidence in a prospective study of monozygotic twins of patients was approximately constant at 1.3% per year (77 cases), again about 0.7% per breast. At ages older than a patient's age at diagnosis, her mother and sisters have an incidence of 0.3-0.4% per year. Above the index patient's age at diagnosis, the rate in relatives shows no temporal trend and is independent of the patient's age at diagnosis. A statistically simple explanation is that incidence in susceptible women increases to a high constant level by a predetermined age that varies between families, but this seems inconsistent with conventional models of carcinogenesis and susceptibility. The very high incidence in monozygotic twins of patients indicates that a high proportion, and perhaps the majority, of breast cancers arise in a susceptible minority of women.

Does monozygotic twinning occur in mice?

Published reports suggest that the incidence of monozygotic twinning in women is increased after hormonally induced ovulation. Since some statistical evidence exists to indicate that monozygotic twinning may also occur in mice, we attempted to devise a mouse system in which the incidence of such twinning could be compared after spontaneous versus hormonally induced ovulation, in order to analyse the developmental basis of such an effect. We used phenotypic identity in litters segregating for ten genetic loci (not all independent) to indicate possible twin pairs. DNA finger-printing using three human minisatellite probes was then performed blind on these pairs and on sibling controls. From a total of over 2000 mice born, 40 apparently identical pairs were identified, on which DNA finger-printing was successfully carried out on 35 pairs. All proved to be derived from different zygotes. We conclude that monozygotic twin pairs are either extremely rare in the stock of mice that we studied, or have such reduced viability that their chance of surviving to weaning is low.

Diagnosis of trisomy 18 in monozygotic twins by cordocentesis

The incidence of monozygotic twins with trisomy 18 is 1 in 1,000,000 births. We report a case diagnosed prenatally with lymphocyte culture from fetal blood samples obtained by cordocentesis. Fetal growth lag and structural malformations detected by ultrasonography indicated chromosomal abnormality. A saline solution infusion technique ensured that cordocentesis obtained a sample from each twin.

CANCER BIOLOGY: COMPARATIVE and GENETIC*

CANCER BIOLOGY: COMPARATIVE and GENETIC*