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Twin-twin transfusion syndrome (TTTS) is a serious complication in monochorionic (MC) pregnancies. Fetoscopic laser surgery (FLS) is the primary treatment for advanced TTTS, but managing Quintero stage I TTTS is still controversial. We conducted an observational study evaluating the 2-year neurodevelopment of fetuses, which underwent FLS for stage I TTTS, compared with advanced TTTS and uncomplicated monochorionic diamniotic twins (MCDTs). The study included 156 children: 14 in stage I TTTS group, 28 in advanced TTTS group, and 114 in uncomplicated twin group. In stage I TTTS, 92.9% showed normal neurodevelopment, with no severe neurological impairments observed. These results were comparable with uncomplicated twins (92.1% normal neurodevelopment, P =.921, adjusted odds ratio [aOR] = 1.56, 95% confidence interval [CI] = 0.42-5.79; 1.8% severe impairment, P =.617). Advanced TTTS had a non-significant lower rate of normal neurodevelopment (89.3%, P =.710, aOR = 1.31, 95% CI = 0.12-14.87). In conclusion, FLS for stage I TTTS shows favorable long-term neurodevelopmental outcomes, similar to uncomplicated MC pregnancies. [ABSTRACT FROM AUTHOR]

It is often argued that certain metaphysical complications surrounding the phenomenon of monozygotic twinning force us to conclude that, prior to the point at which twinning is no longer possible, the zygote or early embryo cannot be considered an individual human organism. In this essay, I argue, on the contrary, that there are in fact several ways of making sense of monozygotic twinning that uphold the humanity of the original zygote, but also that there is no easy answer to what happens when the human zygote twins. All of the options available carry with them one or more surprising, alarming, or otherwise counterintuitive implications. All things considered, I conclude that the "budding option," according to which the original human organism present before twinning carries on as one of the resulting embryos but not the other, is the most plausible explanation of what happens when a human zygote twins. [ABSTRACT FROM AUTHOR]

Aims: To explore whether blastocyst morphology [blastocyst stage, inner cell mass (ICM), and trophectoderm (TE) grading] impacts the occurrence of monozygotic twinning (MZT) after single blastocyst transfer (SBT).Materials and methods: A single-center retrospective cohort study was conducted including all clinical pregnancies after single blastocyst transfer between January 2015 and September 2021 (n = 9229). Blastocyst morphology was assessed using Gardner grading system. MZT was defined as more than one gestational sac (GS), or two or more fetal heartbeats in a single GS via ultrasound at 5–6 gestational weeks.Results: The overall MZT rate was 2.46% (227 of 9229 cases), of which was the highest in blastocysts of grade A TE and lowest in those with grade C TE (grade A: B:C = 3.40%:2.67%:1.58%, p =.002). Higher risk of MZT pregnancy was associated with higher trophectoderm grading [A vs. C: aOR, 1.883, 95% CI 1.069–3.315, p =.028; B vs C: aOR, 1.559, 95% CI 1.066–2.279, p =.022], but not extended culture in vitro (day 5 vs. day 6), vitrification (fresh vs. frozen-thawed ET), assisted hatching (AH), blastocyst stage (stage 1–6) or ICM grading (A vs. B).Conclusions: We conclude that TE grade is an independent risk factor of MZT after single blastocyst transfer. Blastocysts with high-grade trophectoderm are more liable to obtain monozygotic multiple gestation. [ABSTRACT FROM AUTHOR]

Aims: To explore whether blastocyst morphology [blastocyst stage, inner cell mass (ICM), and trophectoderm (TE) grading] impacts the occurrence of monozygotic twinning (MZT) after single blastocyst transfer (SBT).Materials and methods: A single-center retrospective cohort study was conducted including all clinical pregnancies after single blastocyst transfer between January 2015 and September 2021 (n = 9229). Blastocyst morphology was assessed using Gardner grading system. MZT was defined as more than one gestational sac (GS), or two or more fetal heartbeats in a single GS via ultrasound at 5–6 gestational weeks.Results: The overall MZT rate was 2.46% (227 of 9229 cases), of which was the highest in blastocysts of grade A TE and lowest in those with grade C TE (grade A: B:C = 3.40%:2.67%:1.58%, p = .002). Higher risk of MZT pregnancy was associated with higher trophectoderm grading [A vs. C: aOR, 1.883, 95% CI 1.069–3.315, p = .028; B vs C: aOR, 1.559, 95% CI 1.066–2.279, p = .022], but not extended culture in vitro (day 5 vs. day 6), vitrification (fresh vs. frozen-thawed ET), assisted hatching (AH), blastocyst stage (stage 1–6) or ICM grading (A vs. B).Conclusions: We conclude that TE grade is an independent risk factor of MZT after single blastocyst transfer. Blastocysts with high-grade trophectoderm are more liable to obtain monozygotic multiple gestation.

Assisted reproductive technology is a crucial factor that increases the incidence of monozygotic twinning in humans. This article discusses the impact of various indicators in assisted reproductive technology studies on pregnancy outcomes, especially studies with a large number of clinical cases. Furthermore, three rare cases in multiples pregnancy are discussed: fetus papyraceous of a pair of male monozygotic twins in a set of triplets, two pairs of sesquizygotic twins with sex-discordance, and rare conjoined triplets. [ABSTRACT FROM AUTHOR]

The rate of monozygotic twinning (MZT) has seen a gradual increase in recent years. Numerous parameters involved in ART procedures are blamed for this surge, even though the exact explanation is as yet unknown. Our study's objectives were to determine the risk variables for monozygotic twinning after ART and to estimate their prevalence. We examined 25,794 IVF cycles for the incidence of monozygotic twinning in this observational analysis. Our study, which was carried out across seven tertiary IVF centres over the course of four years, found an overall MZT rate of 0.37% per embryo transfer procedure and 0.88% of all pregnancies. Monozygotic twinning was more commonly seen in fresh single-embryo transfer (SET) and blastocyst transfer cycles. Larger multicentre studies are needed to explore the potential risk variables. [ABSTRACT FROM AUTHOR]

Conjoined twins (Siamese twins) represent the rarest form of twin pregnancy. Reported here are two rare cases of conjoined term twins presented to the department of Obstetrics and Gynaecology within 3 months. The first case, 32 years of gravida 6 parity 5 referred from periphery after full trial of labour following multi-organ dysfunction and term intrauterine dead twins. Intraoperatively it was dead conjoined thoraco-omphalopagus females. The patient died after 3 days following multiorgan dysfunction syndrome and disseminated intravascular coagulation. The second case, 22 years gravida 2 parity 1 also referred from periphery in second stage of labour with diagnosis of 39 weeks intrauterine dead twins with obstructed labour, delivered by caesarean with intraoperative conjoined dead females of thoracophagus type. Twins are high-risk pregnancy. This rare diagnosis with complications could have been prevented by regular antenatal checkups, ultrasonography performed by radiologists and early referral antenatally in labour along with multidisciplinary approach.

Whether assisted hatching (AH) is associated with a higher incidence of monozygotic twinning (MZT) in women undergoing assisted reproductive technology remains controversial; the aim of the study was to demonstrate the relationship between AH and MZT. A total of 8900 clinical pregnancies were selected among embryo transfer cycles from January 2011 to October 2019. Women receiving day (D) 3 embryos were divided into groups A-C: group A (n = 1651) and group B (n = 1045) included women aged ≤37 or ≥38 years, respectively, with zona pellucida (ZP) thinning; group C (n = 3865) included women aged ≤37 years without AH. Women aged ≤37 years who underwent blastocyst transfer and/or blastocyst ZP breaching were included in group D (n = 2339). The incidence of MZT was compared among groups A, B and C, and between groups C and D. The incidence of MZT in group B (2.2%) was significantly higher than in group A (1.0%), especially following intracytoplasmic sperm injection (ICSI), while the incidence of MZT in group A (1.0%) was significantly lower than in group C (2.2%). The MZT rate with in vitro fertilization was higher in group D (2.8%) than in group C (2.2%), but the MZT rate following ICSI was not significantly different between the two groups. ZP thinning of D3 embryos may increase the risk of MZT in older women (≥38 years), but decrease it in younger women (≤37 years). ZP breaching may be useful to reduce the incidence of MZT in ICSI-generated blastocysts. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to explore specific factors that predispose to monozygotic twinning (MZT) at the blastocyst stage. Methods: This was a retrospective observational study of a cohort of 2863 pregnancies after single blastocyst transfer (SBT) between January 2011 and June 2019 in our hospital. MZT pregnancy was identified as the number of fetuses exceeded the number of gestational sacs (GSs) by transvaginal ultrasound at 6–7 gestational weeks. The incidences of MZT regarding the maternal age at oocyte retrieval, paternal age, ovarian stimulation protocol, fertilization method, endometrium preparation protocol, vitrified day, and the Gardner grading of the blastocyst were calculated. The serum estrogen (E2), progesterone (P) levels, endometrium thickness and serum hCG levels on day 11 after embryo transfer (ET) were compared between the MZT and singleton pregnancies. Statistical analyses were used appropriately. Results: Fifty-one MZT pregnancies (1.78%) were identified. The only significant differences observed between MZT and singleton pregnancies were the proportion of TE grade (P = 0.022) and the hCG levels on day 11 after ET (P = 0.003). Multivariate logistic regression revealed that trophectoderm (TE) grade was an independent factor affecting MZT, the adjusted odds ratios (aORs) of grade A and B TE were 5.46 [95% confidential interval (CI) 1.48–20.16, P = 0.011) and 3.96 (95% CI 1.17–13.40, P = 0.027) compared to grade C respectively. There were no significant associations between the parental age, fertilization method, ovarian stimulation protocol, endometrium preparation protocol, vitrified day, expansion stage, inner cell mass (ICM) grade and MZT. Conclusions: TE grade is associated with MZT at the blastocyst stage, potentially mediated via increased secretion of hCG from more well developed TE. Increased hCG secretion in turn may prolong the implantation window to support the embryo splitting. [ABSTRACT FROM AUTHOR]

Amyoplasia is a very specific, nongenetic clinically recognizable form of arthrogryposis, representing about one‐third of individuals with arthrogryposis surviving the newborn period. There is a markedly increased number of individuals with Amyoplasia who are one of monozygotic (MZ) twins, with the other twin being normal. Thus, it would appear that Amyoplasia is definitely associated with and may be caused by an MZ twinning event. The twin–twin transfusion seen in MZ twins could play an etiologic role in producing Amyoplasia. In this article, Amyoplasia twinning is compared to twinning in other forms of arthrogryposis. The accompanying paper examines various types of MZ twinning (Hall, 2021). Amyoplasia is primarily associated with spontaneous MZ twinning. [ABSTRACT FROM AUTHOR]

Purpose: To compare monozygotic twinning (MZT) rates in patients undergoing fresh embryo transfer (ET) and frozen embryo transfer. Methods: All clinical pregnancies after single ET carried out in our IVF center between 2014 and 2018 (n = 8459) were retrospectively analyzed for the incidence of MZT. MZT rate was compared in women who underwent fresh ET (n = 3876) and frozen ET (n = 4583). Results: There was a total of 120 MZT identified in the fresh ET group (3.10%) and 103 MZT in the frozen ET group (2.25%), which was significant (p = 0.015). In the univariate analysis, the risk of MZT was decreased with frozen embryo transfer (OR 0.72; 95% CI, 0.55–0.94, p = 0.016) and increased with mild stimulation protocol in the fresh cycle (OR 1.90; 95% CI, 1.04–3.45, p = 0.036). Multivariable logistic regression revealed that frozen embryo transfer was associated with a significant decrease risk of MZT (adjusted OR 0.66; 95% CI, 0.46–0.90, p = 0.011). Conclusions: Frozen ET is associated with a lower risk of MZT. [ABSTRACT FROM AUTHOR]

When a human being comes into existence is crucial in bioethics. Conceptionism is the view that a human being comes into existence at conception. The twinning argument is an influential objection to this view. All versions of the twinning argument rely on a metaphysics of material objects, namely, endurantism. Given this, a strategy for defending conceptionism against the twinning argument is to deny endurantism and adopt an alternative metaphysics of material objects. A version of this strategy which has been debated in this journal is to adopt perdurantism, or the 'multiple occupancy view', on which monozygotic twins share the zygote region as a temporal part. We present a novel version of this strategy: conceptionists can evade the twinning argument by adopting an exdurantist metaphysics of material objects. We suggest reasons for thinking that this is a plausible and, indeed, preferable way for conceptionists to avoid the twinning argument. [ABSTRACT FROM AUTHOR]

Conjoined twinning occurs in 1/100 of monozygotic twins, 1/50,000 gestations and 1/250,000 live births. It is the consequence of a division event at the primitive streak stage of the human embryonic development, about 13-14 days after fertilisation, in monochorionic monoamniotic gestations. A healthy pregnant woman, Gravida 2 Para 1, was admitted into our Fetal Medicine Unit to perform the first trimester ultrasound. A diagnosis of conjoined parapagus twinning based on ultrasound features was made at 11 weeks of gestation, and the couple decided to terminate the pregnancy. The ultrasound showed two independent skulls and hearts, a shared spine below the thoracic level, and a shared stomach. The pathological findings were slightly different, showing two independent stomachs draining into a common duodenum. The karyotype was 46 XY. Early prenatal ultrasound may provide a window to counsel the family and to offer an early termination of pregnancy.

Study Question: What is the prevalence of multiple pregnancy with zygotic splitting after single embryo transfer (SET)?Summary Answer: The prevalence of multiple pregnancy with zygotic splitting after SET was 1.36%.What Is Known Already: In 2008, the Japan Society of Obstetrics and Gynaecology (JSOG) recommended the adoption of SET to reduce multiple births. Since then, to improve the clinical pregnancy rate, elective SET using blastocyst transfer and frozen-warmed ET has increased. Blastocyst culture and zona pellucida manipulation, including ICSI and AH, have been widely reported as risk factors for monozygotic twinning. However, all these studies may have included cases with dizygotic pregnancies produced by a transferred embryo and a spontaneous conception.Study Design, Size, Duration: A retrospective observational study was performed, based on 937 848 SET cycles in registered ART data from the JSOG between 2007 and 2014. The study was approved by the Registration and Research Subcommittee of the JSOG and Juntendo University Ethics Committee.Participants/materials, Setting, Methods: To identify possible factors affecting the prevalence of zygotic splitting, we identified pregnancies, in which the number of foetuses exceeded the number of gestational sacs (GSs), to restrict our analysis to 'true' zygotic splitting. Multiple logistic regression analysis was performed using singleton pregnancy after SET, as control. P < 0.05 was considered statistically significant.Main Results and the Role Of Chance: Fresh and frozen-warmed SET produced 276 934 clinical pregnancies (29.5%/SET), including 4310 twins (1.56% of pregnancies) and 109 triplets (0.04% of pregnancies). Based on sex analysis of dichorionic twins after SET, the prevalence of multiple pregnancy with zygotic splitting was 1.36%. Statistical analysis revealed that compared to singleton pregnancies zygotic splitting pregnancies were associated with frozen-warmed ET cycles (odds ratio [OR] = 1.34; 95% CI: 1.16-1.55), blastocyst culture (OR = 1.79; 95% CI: 1.54-2.09) or AH (OR = 1.21; 95% CI: 1.08-1.35). In fresh ET cycles, the prevalence rate of zygotic splitting pregnancy after single blastocyst transfer was significantly higher than that after SET cycles with cleavage embryos (OR = 2.20; 95% CI: 1.83-2.66). However, no significant difference in ovarian stimulation and fertilization methods was recognized.Limitations, Reasons For Caution: In the current Japanese ART registry system, data regarding frozen-warmed ET do not include information about ovarian stimulation and fertilization methods. Registration for AH only began in 2010. There is no way of validating if data submitted by clinics is correct.Wider Implications Of the Findings: Clinicians should consider whether to counsel couples about the small increase in the risk of zygotic splitting associated with some embryo manipulations.Study Funding/competing Interest(s): No external funds were used for the study. The authors have no competing interests to declare.Trial Registration Number: None. [ABSTRACT FROM AUTHOR]

Highlights • Our meta-analysis provided an update and stronger evidence that BT is associated with a higher frequency of males and an increased risk of MZT. • Subgroup analysis based on studies after 2009 showed the same results. • Larger number of included studies strengthened the findings. • Clearer source of heterogeneity made the results more persuasive. Abstract Research question Is blastocyst transfer (BT) associated with a higher offspring secondary sex ratio and monozygotic twinning (MZT)? Design A systematic search of PubMed/MEDLINE, Embase, Web of Science, Cochrane Library and Google Scholar databases was carried out for studies published between 1995 and May 2017 using relevant keywords and a meta-analysis performed on selected studies. The analysis was performed using Stata 12.0; odds ratios (OR) and 95% confidence intervals (CI) were used to assess the results for binary studies. Subgroup analyses and meta-regression were also conducted. Results Twenty-six studies published between 2001 and May 2017 (sex ratio: 13, MZT: 12, and both sex ratio and MZT: 1) were identified. The analysis showed a significantly higher M/F ratio at birth (OR = 0.89, 95% CI: 0.86 to 0.93, I 2 = 19.8%) and a higher risk of MZT (OR = 0.37, 95% CI: 0.22 to 0.60, I 2 = 75.2%) after BT compared with cleavage-stage embryo transfer (CT). Furthermore, a subgroup analysis was performed based on studies published after 2009; results were found to be consistent with the 2009 meta-analysis. Conclusions This meta-analysis provides an update and stronger evidence to support the observation that BT is associated with a higher proportion of males and an increased risk of MZT. In clinical practice, these BT-associated neonatal outcomes should be taken into account when counselling infertility patients. [ABSTRACT FROM AUTHOR]

Objective: To identify the incidence and risk factors associated with IVF-conceived monozygotic twinning (MZT).Design: Retrospective study.Setting: Academic hospital.Patient(s): A total of 3,463 women with clinical pregnancies between January 2014 and February 2015 were analyzed.Intervention(s): None.Main Outcome Measure(s): The measures were the incidence of MZT based on the number of embryos that were replaced, type of insemination method (conventional IVF or intracytoplasmic sperm injection [ICSI]), with or without the use of assisted hatching (AH), and day of embryo transferred in fresh and frozen cycles.Result(s): Ninety-three women (2.69%) with MZT were observed. No statistically significant differences were observed in the cycle parameters of fresh or frozen cycles between MZT and other non-MZT pregnancies. Specific IVF procedures or techniques, such as the number of embryo replaced, zona pellucida manipulation (ICSI and AH), and freeze-thaw procedure, did not significantly increase the rate of MZT, except for the day of embryo transferred. Compared with day 3 transferred, day 4 and 5/6 transferred showed an increased probability of MZT (odds ratio [OR], 2.73; 95% confidence interval [CI], 1.16-6.42 for day 4 transferred and OR, 3.68; 95% CI, 2.29-5.93 for day 5/6 transferred).Conclusion(s): Extended culture (advanced embryo stage) in fresh and frozen cycles appeared to be associated with increased rates of MZT. The effect of the number of embryos transferred, ICSI and AH, and freeze-thaw procedures on the risk for MZT was not demonstrated. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of assisted reproductive techniques on the incidence of monozygotic twins (MZT) and the associated pregnancy outcomes. Materials and methods: This was a retrospective study of all in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles with MZT pregnancies in our center from January 2001 to December 2011. The diagnosis of MZT pregnancies with their respective placental configurations was based on the results of ultrasonographic examinations performed during either the first or second trimester. The treatment characteristics and outcomes of each IVF cycle were recorded and stored in a computer database. Results: A total of 17 cycles with MZT pregnancies were identified, resulting in an overall incidence of MZT of 1.3%. The incidence of MZT for women aged

Congenital malformations occur in up to 10% of monochorionic twins and are usually discordant. Body wall defect (BWD) is a rare entity of very low prevalence, defined as a combination of various malformations, including fetal body mutilations of thoracic and/or abdominal organs that can be caused by amniotic rupture early in embryonic development. Sirenomelia is a form of caudal regression syndrome that presents with lower limb fusion, among other anomalies. In this report, we will present a second trimester monochorionic diamniotic pregnancy, with BWD-abdominoschisis in one fetus and sirenomelia in the other one. Amniotic bands could not be found. Of particular importance in respect to both malformations is the timing of the insult that could have caused both anomalies. [ABSTRACT FROM AUTHOR]

Monozygotic twins are two individuals derived from one sperm and one egg; dizygotic twins are individuals born together but originating from different eggs fertilized by different sperms. Dizygotic twinning rates vary in different populations but have risen in the last 30 years on account of ovarian stimulation and the increasing tendency to postpone childbearing. Iatrogenic ovarian stimulation induces the simultaneous growth of multiple follicles leading to the ovulation of more than one egg and hence multiple fertilization. Milder forms of ovarian stimulation in intrauterine insemination (IUI) cycles and the choice of single embryo transfer (SET) for in vitro fertilization (IVF) cycles help prevent iatrogenic twinning. The risk of dizygotic twinning linked to postpone childbearing and the higher follicle-stimulating hormone (FSH) concentration poorly controlled by an older ovary is harder to change in the short term. As increasing number of women delay reproduction, for understandable social reasons, the ovarian/pituitary system in women older than 25 generates 5–8 additional twins per 1000 births every additional year of age. A new social strategy to encourage reproduction in young couples would be needed to influence the current widespread tendency.

Objective: To examine the relationship between the inner cell mass (ICM) grade and its morphological configuration on the occurrence of monochorionic diamniotic (M-D) twinning.Design: Retrospective embryo cohort study.Setting: Private IVF clinic.Patient(s): Evaluation of frozen-thawed single blastocyst transfers with hormone replacement treatment in 8,435. This cohort included 71 blastocysts and their ICMs observed by time-lapse photography.Intervention(s): Any changes in configuration of the ICMs observed by time-lapse photography were analyzed retrospectively.Main Outcome Measure(s): The amount of loosening of blastomeres within the ICM was evaluated by time-lapse observations. The number of cells that were involved in the loosening process was also assessed. Both of these parameters were correlated with the type of monozygotic twinning that eventuated.Result(s): The M-D twinning incidence resulting from blastocysts with a high grade ICM (grade A) were transferred was 0.38% (3/796), whereas it was significantly higher, 1.38% (34/2,463), when blastocysts with a poorer (B and C) grade ICM were transferred. Among 71 transferred frozen-thawed blastocysts that were studied with time-lapse photography, there were two dichorionic diamniotic and one M-D twins. Careful observations of the embryo that resulted in the one M-D case, revealed that the ICM acquired a looser appearance due to decompaction of at least eight cells. This type of decompaction was not observed in the ICMs of other transferred blastocysts.Conclusion(s): The occurrence of M-D twinning may be avoided by excluding blastocysts that contain decompacting ICMs. [ABSTRACT FROM AUTHOR]

Objective To describe a case of monozygotic twinning with asymmetric development following a single fresh embryo transfer as part of an intracytoplasmic sperm injection (ICSI) treatment. Secondarily, to report the incidence of monozygotic twinning at the IVI (Instituto Valenciano de Infertilidad) clinics. Design Case report. Setting Private fertility centers. Patient(s) A 33-year-old woman with a 2-year history of primary infertility. Intervention(s) Controlled ovarian hyperstimulation and ICSI treatment with single-embryo transfer. Main Outcome Measure(s) Incidence of monozygotic twinning at the IVI clinics. Result(s) We report a twin pregnancy after a single-embryo transfer. Twins were dichorionic and diamniotic. One fetus had a 6-day delay in its growth compared with the other when observed by ultrasound. Two female infants were delivered, and despite presenting congenital diseases, they were successfully treated and evolved correctly. A subsequent DNA analysis confirmed that the infants were monozygotic. Furthermore, we estimated a monozygotic twinning rate of 1.17% at the IVI clinics, taking into account those cases in which two or more embryos with heart beats were observed by ultrasound scanning after single-embryo transfers. Conclusion(s) Ultrasound scans performed during pregnancy suggested a possible dizygotic origin of the twins, but DNA analysis performed after birth established that they were monozygotic. Genetic analysis is the only valid tool to confirm if like-sex dichorionic twins are monozygotic or dizygotic. [ABSTRACT FROM AUTHOR]

Purpose: To assess the incidence of monozygotic twinning (MZT) among cases undergoing assisted reproductive technology (ART) treatment. Methods: We performed a retrospective observational study and analyzed the data of patients who were registered in the national ART registry system of Japan from January to December 2010; only the data of patients with single embryo transfer (ET) were included. Results: Of 30,405 pregnancies, 425 resulted in MZT following fresh and frozenthawed ET. The MZT incidence among women undergoing ART was 1.4 %. Multiple logistic regression analysis indicated that cases undergoing fresh and frozen-thawed ET, blastocyst transfer had a significantly increased MZT rate ( P < 0.01). Assisted hatching (AH) and frozen-thawed ET and maternal age did not significantly affect the MZT incidence. Of 8510 fresh ET pregnancies, 104 resulted in MZT. Multiple logistic regression analysis indicated that blastocyst transfer significantly increased the MZT rate in cases undergoing fresh ET. Ovarian stimulation, intracytoplasmic sperm injection, AH, and maternal age did not significantly affect the MZT incidence. Conclusions: Blastocyst transfer was associated with an increased MZT incidence. We have to be aware of the potential risk of MZT caused by blastocyst transfer. However, further studies are required to assess the correlation among specific AH types, embryo culture conditions, and MZT incidence. [ABSTRACT FROM AUTHOR]

Objective: To study the incidence and potential causes of monozygotic twins after in vitro fertilization and embryo transfer (IVF-ET). Methods: A retrospective study was performed on women carrying monozygotic twins (MZTs) after conventional IVF-ET treatment at the Third Affiliated Hospital of Guangzhou Medical College in China from January 2003 to May 2009. The incidence and the miscarriage rate for MZTs following IVF-ET were examined in relation to maternal age, duration of infertility, type and dose of hormone treatment, conventional IVF-ET cycles versus intracytoplasmic sperm injection (ICSI) cycles, the use of fresh or frozen-thawed embryos, and day (post-fertilization) of embryo transfer. Results: Sixteen MZT pregnancies occurred in 2 161 patients (incidence of 0.74%), of which 5 miscarried (31.25%). No significant difference was found between MZT and non-MZT groups in terms of maternal age, duration of infertility, duration of gonadotropin (Gn) administration, dosage of Gn, number of oocytes retrieved, number of oocytes fertilized, or number of embryos transferred (P>0.05). The incidence of MZT was not statistically different between conventional IVF-ET cycles and ICSI cycles, between fresh embryos transfer cycles and frozen-thawed embryo cycles, or between different transfer days (P>0.05). Conclusions: The incidence of MZTs following IVF-ET treatment greatly exceeds that observed following spontaneous conception. Intracytoplasmic sperm injection, frozen-thawed procedures, and embryo transfer on different days were not correlated with an increased incidence of MZT pregnancies. [Copyright &y& Elsevier]

Objective: To compare the incidence of monozygotic twinning between cleavage-stage and blastocyst-stage embryo transfer in a large cohort of patients undergoing single embryo transfer. Design: Retrospective study. Setting: Dutch-speaking Free University of Brussels. Patient(s): This study covered the period between July 2003 and December 2005. 1,951fresh IVF/ICSI cycles in which single embryo transfer was performed were retrospectively reviewed. Only the first cycle of each patient was included. Intervention(s): Five hundred eighty seven (n = 587) cycles that resulted in clinical pregnancies were identified; 308 after single day-3 embryo transfer and 271 after single blastocyst transfer. Main Outcome Measure(s): The incidence of monozygotic twinning. Result(s): Overall, 13 cases (2.2%) of monozygotic twinning were observed, 2.6% in the cleavage-stage group (n = 8/308) and 1.8% in the blastocyst group (n = 5/271). No statistically significant differences were observed in the probability of monozygotic twinning between the Cleavage-stage and the Blastocyst group (difference: +0.8%; 95% CI, –1.97 to +3.41). All of these pregnancies resulted in the delivery of 24 healthy babies. The crude odds ratio for the incidence of monozygotic twinning after day-5 embryo transfer was calculated to be 0.71 (95% CI, 0.23–2.18). Conclusion(s): To investigate the potential association between the day of embryo transfer (day 3 or 5) and the incidence of monozygotic twinning, the clinical pregnancies analyzed should have been established after single embryo transfer. The current study represents the first methodologically appropriate study attempting to investigate the above research question. Our findings support that opting for blastocyst transfer does not increase the probability for monozygotic twins. [Copyright &y& Elsevier]

Theorems, proofs, laws and rules are commonly named according to the presumed investigator, but often earlier investigators have contributed substantially to the findings. One example of this is Hellin's law, which was named after Hellin, although he was not the first to discover it. In research on twinning and higher multiple maternities, the law has played a central role because it is approximately correct, despite showing discrepancies that are difficult to explain or eliminate. Several improvements to this law have been proposed. In this study, we re-examine some old papers to provide an overview of the scientists who have contributed to the genesis and the improvements of this law. In addition, we consider more recent contributions in which Hellin's law has been discussed and evaluated. It has been mathematically proven that Hellin's law does not hold as a general rule. However, most studies are based on empirical rates of multiple maternities, ignoring random errors. Such studies can never confirm the law, but only serve to identify errors too large to be characterized as random. [ABSTRACT FROM AUTHOR]

Background: An increased incidence of monozygotic twinning after a blastocyst transfer has been previously reported in assisted reproductive technology treatment. It is uncertain whether this phenomenon is due to the extended culture time, culture medium, or inherent blastocyst parameters.Objective: This study aimed to investigate the association between blastocyst parameters (in vitro culture time, blastocyst stage, and inner cell mass and trophectoderm grading) and the incidence of monozygotic twinning after assisted reproductive technology.Study Design: This was a retrospective cohort study employing data from a multicenter, large, electronic database from 4 academic hospitals. All clinical pregnancies after a single blastocyst transfer between January 2014 and February 2020 were included. Blastocyst morphology was evaluated based on the Gardner grading system, considering the blastocyst stage, and inner cell mass and trophectoderm grading (grades A, B, and C). Monozygotic twinning was defined as ≥2 fetal heartbeats in a single gestational sac or 2 gestational sacs with sex concordance at birth. The multivariable predicted marginal proportions from logistic regression models were used to compute adjusted relative risks for the association between blastocyst parameters and the incidence of monozygotic twinning.Results: The overall monozygotic twinning rate was 1.53% (402 of 26,254 cases). The monozygotic twinning was not associated with the culture time in vitro (day 5 vs day 6) or blastocyst stage (early, blastocyst, expanded, hatching, and hatched). Alternatively, monozygotic twinning was associated with lower inner cell mass grading (B vs A: adjusted relative risk, 1.67 [95 % confidence interval, 1.28-2.25]; C vs A: adjusted relative risk, 1.98 [95% confidence interval, 1.18-3.11]) and higher trophectoderm grading (B vs C: adjusted relative risk, 1.38 [95% confidence interval, 1.03-1.92]; A vs C: adjusted relative risk, 2.14 [95% confidence interval, 1.45-3.20]). The incidence of monozygotic twinning was the lowest in blastocysts with grade A inner cell mass and grade B or C trophectoderm (0.82%, as the reference) and the highest in blastocysts with grade B or C inner cell mass and grade A trophectoderm (2.40%; adjusted relative risk, 2.62; 95% confidence interval, 1.60-4.43). The incidence of monozygotic twinning in blastocysts with consistent inner cell mass or trophectoderm grading was somewhere in between (both A: 1.58%; adjusted relative risk, 1.86 [95% confidence interval, 1.23-3.04]; both B or C: 1.59%; adjusted relative risk, 1.84 [95% confidence interval, 1.29-2.90]).Conclusion: Higher risk of monozygotic twinning was associated with blastocyst morphology specific to those blastocysts with loosely arranged inner cell mass cells combined with tightly packed trophectoderm cells. [ABSTRACT FROM AUTHOR]

Objective: The purpose of our study is to compare the occurrence of monozygotic twinning (MZT) from blastocyst transfer (BT) in our program between an earlier and more recent time period. Design: Retrospective. Setting: Academic IVF practice. Patient(s): All pregnancies conceived between March 2002 and December 2005 (N = 932) in our program were compared to pregnancies conceived before March 2002 (N = 554), which were the subject of a previous study. Intervention(s): None. Main Outcome Measure(s): The incidence of MZT with day 3 embryo transfer and BT were compared between the study and control groups. Result(s): During the study period, the rate of MZT was not significantly different for BT at 2.3% (9/385) compared to day 3 embryo transfer at 1.8% (10/547). This rate of 2.3% for BT was significantly lower than the rate of 5.6% (11/197) reported at our institution for BT before March 2002. Conclusion(s): Our study suggests that the risk of MZT with BT is significantly lower in the more recent time period and is in the range of what is seen with cleavage stage transfer. It is likely that improvements in culture systems as experience is gained with BT played a role. [Copyright &y& Elsevier]

A central problem in research on twins is the estimation of the rates of monozygotic and dizygotic twin maternities. The estimation usually follows Weinberg's differential rule. According to this rule, the rate of dizygotic twinning is twice the rate of twin maternities in which the twins are of opposite sex. The monozygotic twinning rate is the difference between the rates of same-sex and opposite-sex twin sets. Weinberg's differential rule is implicitly based on the assumptions that the probability of a male equals the probability of a female and that the sexes in a dizygotic twin set are independent. Although Weinberg's differential rule has been the target of continuing discussions, the reliability of these assumptions has never been conclusively verified or rejected. In this study we present new variance formulas for the monozygotic and dizygotic twinning rates obtained using Weinberg's differential rule and stress that these new formulas have to be used. We analyze the accuracy of Weinberg's differential rule by considering alternative attempts. Especially, we build a general likelihood function and show that the maximum-likelihood estimates differ only slightly from the rates obtained using Weinberg's differential rule. In addition, our methods are applied to twinning data from Finland and Sweden. We compare our results with findings in the literature. In conclusion, our findings indicate that Weinberg's differential rule is rather robust and that despite its simplicity, it gives reliable results when official birth registers are analyzed. [ABSTRACT FROM AUTHOR]

From fertilization to approximately the sixteenth day of development, human embryonic cells are said to have the capacities of totipotency and monozygotic twinning, both of which are problematic to a theory of ensoulment at fertilization. In this article I will address the problems which these capacities pose to such a theory and present an interpretation of the biological data which renders ensoulment at fertilization more plausible. I will then argue that not only is an ensoulment theory consistent with current biological data on the human embryo, but it may offer an explanation for the phenomencon of monozygotic twinning. [ABSTRACT FROM AUTHOR]

Purpose: To present the occurrence of a monozygotic bichorionic twinning after the transfer of a single frozen/thawed embryo has undergone assisted zona hatching (AZH), using a non contact laser. Methods: A 33-year-old woman who underwent single frozen embryo replacement (FER). Before transfer, the patient was treated with GnRH agonist and with substitutive therapy (estrogens and progesterone). Conclusions: We are absolutely certain that we are reporting a monozygotic bichorionic pregnancy: a single frozen/thawed embryo was transferred and no concomitant spontaneous conception was possible. Moreover, molecular biology assessment for polymorphisms confirmed clinical findings. The possibility of the occurrence of a monozygotic bichorionic twinning after the transfer of a single frozen/thawed embryo should be borne in mind and its incidence will have to be studied further. [ABSTRACT FROM AUTHOR]

Background. Because of complications related to multiple pregnancies after in vitro fertilization this pathology represent a real problem. Intracytoplasmic sperm injection (ICSI) may lead to higher risk in developing monozygotic pregnancies. We sought to investigate whether the multiple pregnancies after ICSI differ of those consecutive to classical in vitro fertilization (IVF) and if counseling for transfering one or at most two embryos is efficient in preventing multiple pregnancies.Methods. We analyzed retrospectively data concerning the incidence of multiple pregnancies before and after the transfer of limited number of embryos.Results. In transfering two cleaving-stage embryos (day 2) or blastocysts (day 5), when pregnancy rate is high, the incidence of multiple pregnancies is 25 and 17%. After transfer of one blastocyst the highest the pregnancy rate and the lowest the incidence of multiple pregnancies.Conclusions. The best way to avoid multiple pregnancies consist in transferring one or at most two embryos. The monozygotic twin pregnancy we observed was consecutive to the transfer of frozen-thawed blastocyst.

The mechanism of monozygotic multifetal pregnancy and its association with assisted reproductive technology are uncertain. This report presents two cases of dizygotic triplet pregnancy after the transfer of three embryos in utero . The incidence of monozygotic twinning following assisted conception procedures is higher than in the general population. Zonal manipulation may be a major factor in the increased incidence of monozygotic twinning. As both cases followed the conventional in vitro fertilization (IVF), the reason for these monozygotic twinnings might be because of the changes in the zona pellucida in in vitro conditions. In one case, fetuses developed into severe twin-to-twin transfusion syndrome (TTTS), resulting in one intrauterine fetal death at 26 weeks gestation. (Reprod Med Biol 2003; 2: 41–44). [ABSTRACT FROM AUTHOR]

: ObjectiveTo evaluate the incidence of monozygotic twinning (MZT) in pregnancies conceived after blastocyst transfer compared to cleavage-stage transfer.: DesignRetrospective study.: SettingUniversity 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. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]