The association between the number of oocytes retrieved for IVF, perinatal outcome and obstetric complications.

HUMAN REPRODUCTION(2018)

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Abstract
STUDY QUESTION: Is there an association between the number of oocytes retrieved for IVF, and perinatal and obstetric outcomes? SUMMARY ANSWER: No significant association was found between the number of oocytes retrieved and perinatal outcomes, while an association was found for placenta praevia and male gender. WHAT IS KNOWN ALREADY: Previous studies have shown that between 6 and 15 oocytes retrieved is optimal for the live birth rate in fresh cycles. In a recent study, we showed that the cumulative live birth rate, including fresh and all cryopreservation cycles following one OPU, increases by the number of oocytes retrieved, up to approximately 20 oocytes. However, there was also an increase in serious side effects such as severe ovarian hyperstimulation syndrome (OHSS). A few studies, with contradictory results, have investigated whether the number of oocytes retrieved might also be associated with negative obstetric and perinatal outcomes. STUDY DESIGN, SIZE, DURATION: A retrospective population-based registry study including all singleton babies born after fresh IVF cycles from 2002 to 2015 (n = 27 359) in Sweden. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data on treatment characteristics from the Medical Birth/IVF Registry and the Swedish National Quality Registry of Assisted Reproduction, including all fresh IVF cycles performed in public or private infertility clinics during the study period and resulting in singleton deliveries, were cross-linked to the Medical Birth Registry and the National Patient Registry for maternal and neonatal outcome. Data on educational level, ethnicity and paternal age were obtained through cross-linking to Statistics Sweden. Oocyte donation cycles were excluded. Main perinatal outcome variables were preterm birth (PTB < 37 gestational weeks), very PTB (< 32 gestational weeks), small for gestational age (SGA: < 2 SD), peri/neonatal death and major birth defects. Main obstetric outcome variables were hypertensive disorders of pregnancy and placenta praevia. Univariable and multivariable analyses were used to explore the association between the number of oocytes retrieved and outcome variables. Adjustments were performed for maternal age, parity, smoking, BMI, cause of infertility, maternal educational level, maternal country of birth, treatment period, embryo stage, fertilization method (IVF/ICSI), number of embryos transferred, OHSS and vanishing twin. MAIN RESULTS AND THE ROLE OF CHANCE: The number of oocytes retrieved was analyzed as a continuous variable as well as categorized as < 10, 10-14, 15-19 and > 20 oocytes. A number of between four and nine oocytes was used as a reference. Single embryo transfer was performed in 20 910 (76.4%) of the cycles. Blastocyst transfer was performed in 3478 (12.7%) and cleavage stage embryo transfer was performed in 23 881 (87.3%) of the cycles. No significant association was observed between the number of oocytes retrieved (continuous variable) and PTB (adjusted odds ratio [AOR] 1.002, 95% CI 0.994-1.011), very PTB (AOR 1.013, 95% CI 0.994-1.032), SGA (AOR 0.998, 95% CI 0.988-1.009), peri/neonatal death (AOR 1.008, 95% CI 0.975-1.043) or major birth defects (AOR 1.009, 95% CI 0.998-1.020). Concerning obstetric outcomes, a significant association was found for placenta praevia (AOR 1.021, 95% CI 1.005-1.037) while no association was found for hypertensive disorders of pregnancy (AOR 0.991, 95% CI 0.981-1.001). Furthermore, a significant association was detected between the number of oocytes retrieved and the secondary outcome variable gender distribution, with a higher rate of males after > 20 oocytes ( AOR 1.126, 95% CI 1.014-1.249). LIMITATIONS, REASONS FOR CAUTION: As in all observational studies, unknown confounders may affect outcomes. WIDER IMPLICATIONS OF THE FINDINGS: These results are reassuring, indicating that there is no association between adverse neonatal outcomes and the number of oocytes retrieved. The association between the number of oocytes and placenta praevia was significant, though weak. The finding of an association with gender should be interpreted with caution. STUDY FUNDING/COMPETING INTEREST(S): Financial support was received through Sahlgrenska University Hospital (ALFGBG-70 940) and the Hjalmar Svensson Research Foundation. None of the authors declares any conflict of interest.
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Key words
Ovarian stimulation,number of oocytes,ovarian response,perinatal outcome,obstetric complications
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