Analysis of biochemical and biophysical risk factors for monozygotic twinning observed within an in vitro fertilization program

Abstract

OBJECTIVE: Identify risk factors for monozygotic twinning (MZT) in an in vitro fertilization (IVF) program. DESIGN: Retrospective study. MATERIALS AND METHODS: IVF records (Jan 2002 - June 2007) were reviewed to identify cycles resulting in clinical pregnancies (intrauterine gestational sac). MZT were identified by records of obstetrical ultrasounds performed 4-6 weeks after oocyte retrieval indicating more gestational sacs and/or fetal cardiac activity than the number of embryos transferred or multiple fetal cardiac activities within a single sac. Cycles were grouped by zona manipulation (ZM: intracytoplasmic sperm injection (ICSI) and/or assisted hatching (AH)) and developmental stage at embryo transfer (ET). MZT rates were compared between groups by χ2. RESULTS: Among 6,731 pregnancies were 189 MZT (2.8%). MZT rates were higher for blastocyst versus cleavage stage ET among cycles with no ZM (p=0.049) and among cycles with any ZM (p=0.022). Among ICSI only cycles, MZT rates were also higher for blastocyst than for cleavage stage ET (p=0.0085). Among cleavage stage ET, MZT rates were higher for any ZM versus no ZM cycles (p=0.043). Higher rates were also noted for AH only (p=0.043) and AH with ICSI (p=0.015) compared to no ZM ET. Among blastocyst stage ET, higher rates of MZT were also seen with any ZM versus no ZM cycles, but this difference was only marginally significant (p=0.077). Compared to cleavage stage ET, blastocyst ET was associated with fewer embryos per ET (2.5 vs 1.9, p<0.0001), higher implantation (25% vs 48%, p<0.0001) and lower high order multiple pregnancy (2.3% vs 1.3%, p=0.0014).Table 1MZT Rate (%) according to ZM and ET stage, sample sizes in parentheses.Stage at ETNo ZMAny ZMICSI onlyAH onlyICSI & AHCleavage1.5 (1047)2.6 (2609)2.0 (1098)3.0 (599)3.2 (912)Blastocyst2.7 (1324)3.9 (1751)3.9 (1101)4.3 (301)3.4 (349) Open table in a new tab CONCLUSIONS: Our results indicate that extended culture with blastocyst stage ET is an independent risk factor for MZT. With cleavage stage ET, MZT risk increases with AH. ZM (either AH or ICSI) may also increase MZT risk with blastocyst ET, but this trend was less conclusive. The small increase in MZT risk associated with blastocyst ET is outweighed by benefits including improved implantation, decreased embryos per ET and decreased risk of high order multiples. With use of extended culture and/or ZM, patients should be counseled on the increased risks of and poor obstetrical outcomes associated with MZT but understand that it is a clinical rarity.