Early spontaneous multiple fetal pregnancy reduction is associated with adverse perinatal outcomes in in vitro fertilization cycles

Petrini, Allison C.; Pereira, Nigel; Lekovich, Jovana P.; Elias, Rony T.; Spandorfer, Steven D.

doi:10.1177/1745505716658898

Cited by 10 publications

(16 citation statements)

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“…Previous studies have compared pregnancy outcomes among ART singletons with VTS to either ART singletons without VTS or ART multiples ( Pinborg et al , 2005 , 2007 ; Shebl et al , 2008 ; Luke et al , 2009 ; Almog et al , 2010 ; Sazonova et al , 2011 ; Davies et al , 2016 ; Petrini et al , 2016 ; Zhou et al , 2016 ). The studies of ART singletons found reductions in birth weight with a vanishing twin ranging from 89 to 373 g ( Pinborg et al , 2005 ; Shebl et al , 2008 ; Almog et al , 2010 ; Sazonova et al , 2011 ; Petrini et al , 2016 ). Two studies reported an increased risk of SGA similar to our findings, with ORs of 1.50 and 2 ( Pinborg et al , 2007 ; Shebl et al , 2008 ).…”

Section: Discussionmentioning

confidence: 99%

“…With regard to IVF/ICSI pregnancies, it is estimated to occur in 12–30% ( Gjerris et al , 2012 ). Furthermore, VTS is associated with adverse pregnancy outcomes for the remaining survivor among both spontaneously conceived ( Evron et al , 2015 ) and ART pregnancies ( Pinborg et al , 2005 , 2007 ; Shebl et al , 2008 ; Luke et al , 2009 ; Almog et al , 2010 ; Sazonova et al , 2011 ; Davies et al , 2016 ; Petrini et al , 2016 ; Zhou et al , 2016 ). Adverse outcomes include higher risk of low birth weight, preterm birth, small for gestational age (SGA) and birth defects.…”

Section: Introductionmentioning

confidence: 99%

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Vanishing twin syndrome among ART singletons and pregnancy outcomes

et al. 2017

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STUDY QUESTIONAmong babies born by ART, do singleton survivors of a vanishing twin have lower birth weight than other singletons?SUMMARY ANSWERVanishing twin syndrome (VTS) was associated with lower birth weight among ART singletons; a sibship analysis indicated that the association was not confounded by maternal characteristics that remain stable between deliveries.WHAT IS KNOWN ALREADYPrevious studies indicate that ART singletons with VTS have increased risk of adverse pregnancy outcomes, compared with other ART singletons. The potential contribution of unmeasured maternal background characteristics has been unclear.STUDY DESIGN, SIZE AND DURATIONThis was a Norwegian population-based registry study, including 17 368 mothers with 20 410 ART singleton deliveries between January 1984 and December 2013.PARTICIPANTS/MATERIALS, SETTING, METHODSThe study population included 17 291 ART singletons without VTS, 638 ART singletons with VTS and 2418 ART singletons with uncertain vanishing twin status. We estimated differences in birth weight and gestational age comparing ART singletons with VTS first to all ART singletons without VTS, and subsequently to their ART siblings without VTS, using random- and fixed-effects linear regression, respectively. The corresponding comparisons for the associations with preterm birth and small for gestational age (SGA) were conducted using random-and fixed-effects logistic regression. The sibling analysis of preterm birth included 587 discordant siblings, while the sibling analysis of SGA included 674 discordant siblings.MAIN RESULTS AND THE ROLE OF CHANCEART singletons with VTS had lower birth weight when compared to all ART singletons without VTS, with an adjusted mean difference (95% CI) of −116 g (−165, −67). When we compared ART singletons with VTS to their ART singletons sibling without VTS, the adjusted mean difference was −112 g (−209, −15). ART singletons with VTS also had increased risk of being born SGA, with an adjusted odds ratio (OR) (95% CI) of 1.48 (1.07, 2.03) compared to all ART singletons without VTS, and 2.79 (1.12, 6.91) in the sibship analyses. ART singletons with VTS were also more likely to be born preterm, although this difference did not reach statistical significance.LIMITATIONS REASONS FOR CAUTIONWe did not have information on maternal socio-economic status, but this factor is accounted for in the sibship analyses. We also had no information on whether fresh or frozen embryos were replaced.WIDER IMPLICATIONS OF THE FINDINGSThe reduction in birth weight and increased risk of SGA in ART singletons with VTS may suggest the presence of harmful intrauterine factors with long-term health impact. While vanishing twins are not routinely observed in naturally conceived pregnancies, loss of a twin is potentially a risk factor for the surviving foetus in any pregnancy. This could be further explored in large samples of naturally conceived pregnancies with the necessary information.STUDY FUNDING/COMPETING INTEREST(S)The authors of this study are supported in part b...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Vanishing twin syndrome among ART singletons and pregnancy outcomes

et al. 2017

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“…First, only ICSI cycles were included in the current study, which reflects up to 80% of the overall patient population undergoing ART at our center. However, it is worthwhile to note that similar trends in PTB and LBW have been reported in patients undergoing in vitro fertilization using smaller sample sizes in internal [45] and external investigations [39,40]. Second, a mean of 3.01 embryos were transferred in the current study.…”

Section: Discussionmentioning

confidence: 56%

Identifying Maternal Constraints on Fetal Growth and Subsequent Perinatal Outcomes Using a Multiple Embryo Implantation Model

et al. 2016

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IntroductionAlthough the majority of singleton births after in vitro fertilization (IVF) are uncomplicated, studies have suggested that IVF pregnancies may be independently associated with low birth weight (LBW), preterm birth (PTB), and perinatal mortality. These outcomes complicate multiple gestations as expected, but have also been reported in singletons. A multiple embryo implantation model allows for assessment of the early in utero environment, and therefore, assessment of any maternal constraints on developing fetuses. We question whether adverse perinatal outcomes associated with assisted reproductive techniques (ART) occur as a result of maternal physiologic adaptations.Patients and MethodsThis is a retrospective, single center study of ART cycles, specifically intracytoplasmic sperm injection (ICSI) cycles during a 16-year period. For each positive pregnancy test 9–11 days after embryo transfer, an ultrasonogram was performed at 7 weeks of gestation to record the number of implanted fetal poles with cardiac activity. Controlled ovarian stimulation (COS), hCG trigger, oocyte retrieval and sperm injection were performed as per our standard protocols. First trimester implantation sites that resulted in live births were defined as “true” to distinguish them from those that spontaneously reduced called “virtual.” Birth outcomes analyzed included birth weight and gestational age at delivery.ResultsA total of 17,415 cycles were analyzed. The average maternal age was 36.9 (±5.0) years. An overall fertilization rate of 73.4% generated approximately 48,708 good quality cleavage-stage embryos. In most patients (92.8%), an average of 3 embryos were transferred. The clinical pregnancy rate was 39.2% (n = 6,281). The overall occurrence of multiple gestations was 38.2% (n = 2,608) consisting of 2,038 twin, 511 triplet, and 59 quadruplet pregnancies. Of these multiple gestations, 18.6% of twin, 54.2% of triplet and 76.3% of quadruplet gestations spontaneously reduced. Failure of the implanted embryo to progress was not related to maternal age. Singleton newborns resulting from multiple implantation sites had lower birth weights (P<0.01) and shorter gestational ages (P<0.01) than those from a single implanted embryo. The number of embryos transferred did not affect the gestational length of singleton newborns. Although the birth weights of singletons from multiple implantation sites (virtual singletons) were lower than true singletons, the birth weight of virtual singletons were comparable to the birth weights of true twin, triplet, and quadruplet live births. Multiple logistic regression revealed that virtual singletons were an independent risk factor for PTB (odds ratio: 4.55, 95% CI 2.23–9.29) and LBW (odds ratio: 3.61, 95% CI 1.78–7.32), even after controlling for the number of oocytes, stimulation protocol type, sperm source, total gonadotropins administered, age, embryo quality, and day of embryo transfer.ConclusionsOur study highlights that embryonic implantation sites during early gestation set the growth profil...

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“…Only patients with live singleton birth were included. The diagnosis of early VT was made based on criteria described by Petrini et al [15]. In brief, patients with a positive β -human chorionic gonadotropin (hCG) level on cycle day (CD) 28 underwent a transvaginal sonogram on CD 49 to record the number of fetal poles with cardiac activity in the respective gestational sacs [15].…”

Section: Methodsmentioning

confidence: 99%

“…The diagnosis of early VT was made based on criteria described by Petrini et al [15]. In brief, patients with a positive β -human chorionic gonadotropin (hCG) level on cycle day (CD) 28 underwent a transvaginal sonogram on CD 49 to record the number of fetal poles with cardiac activity in the respective gestational sacs [15]. Patients with spontaneous in utero reduction of one or more embryos before CD 49 were considered to have an early VT. For this study, we only included embryos that spontaneously reduced within the first trimester.…”

Section: Methodsmentioning

confidence: 99%

Perinatal Risks Associated with Early Vanishing Twin Syndrome following Transfer of Cleavage- or Blastocyst-Stage Embryos

Pereira

Pryor

Petrini

et al. 2016

Journal of Pregnancy

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Objective. To investigate whether the perinatal risks associated with early vanishing twin (VT) syndrome differ between cleavage- or blastocyst-stage embryo transfers (ET) in fresh in vitro fertilization (IVF) cycles. Methods. Retrospective, single-center, cohort study of IVF cycles with fresh cleavage- or blastocyst-stage ETs resulting in a live singleton birth. The incidence of preterm birth (PTB), low birth weight (LBW), and very low birth weight (VLBW) was compared between cleavage- and blastocyst-stage ET cycles complicated by early VT. Results. 7241 patients had live singleton births. Early VT was observed in 709/6134 (11.6%) and 70/1107 (6.32%) patients undergoing cleavage-stage and blastocyst-stage ETs, respectively. Patients in the blastocyst-stage group were younger compared to the cleavage-stage group. The cleavage-stage group had a similar birth weight compared to the blastocyst-stage group. There was no difference in the incidence of PTB (9.87% versus 8.57%), LBW (11.1% versus 11.4%), or VLBW (1.13 versus 1.43%) when comparing the cleavage-stage early VT and blastocyst-stage early VT groups, even after adjustment with logistic regression. Conclusions. Our study highlights that the adverse perinatal risks of PTB, LBW, and VLBW associated with early VT syndrome are similar in patients undergoing cleavage-stage or blastocyst-stage ETs during fresh IVF cycles.

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Early spontaneous multiple fetal pregnancy reduction is associated with adverse perinatal outcomes in in vitro fertilization cycles

Cited by 10 publications

References 23 publications

Vanishing twin syndrome among ART singletons and pregnancy outcomes

Vanishing twin syndrome among ART singletons and pregnancy outcomes

Identifying Maternal Constraints on Fetal Growth and Subsequent Perinatal Outcomes Using a Multiple Embryo Implantation Model

Perinatal Risks Associated with Early Vanishing Twin Syndrome following Transfer of Cleavage- or Blastocyst-Stage Embryos

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