Abstract
Study question
Does embryo vitrification or donor oocytes (DO) alter the histopathology of the placenta in ICSI singleton pregnancies with similar endometrial preparation?
Summary answer
Placentas from programmed cycles had significantly more immune/idiopathic-inflammation with vitrified-thawed embryos versus fresh transfer and significantly more maternal vascular-malperfusion(MVM) in DO versus autologous oocyte(AO) pregnancies.
What is known already
DO pregnancies and frozen embryo transfer(FET) pregnancies with programmed cycles are associated with hypertensive complications. As these complications are linked with abnormal placentation, comparing the placental histopathology in these pregnancies may point to a causative association.
Studies of placental histopathology in DO in comparison to AO pregnancies show a dysregulated immune process and vasculopathy. The hormonal milieu during implantation remains an important confounder.
Placental histopathology in fresh/ frozen cycles has recently shown variable results. To isolate the effect of embryo vitrification on placental histopathology, the donor oocyte model can provide valuable data, which till now is scarcely available.
Study design, size, duration
A prospective cohort study conducted in a tertiary center from 2018–2020.
Placental histopathology, pregnancy-outcomes were studied in 116 ICSI singleton pregnancies≥28 weeks.
Group1-Pregnancies with DO, by FET(n = 32) and freshET(n = 34) were compared to study the effect of embryo-vitrification.
Group2-Pregnancies by DO FET(n = 32) were compared to AO FET(n = 50) to study the effect of DO.
All patients had ICSI, cleavage embryo-transfer, programmed cycles and delivered at the same institute.
The placentas were examined by pathologists (blinded to the ET type).
Participants/materials, setting, methods
116 singleton pregnancies were followed for hypertensive disorders of pregnancy (HDP), preterm delivery(PTD<37weeks) and low birth-weight (LBW<2.5kg).
Placentas were examined for cord mal-insertions
Placental histopathology lesions were classified into 4 groups according to ‘Amsterdam criteria’ infectious-inflammatory, immune/ idiopathic-inflammatory, MVM, fetal vascular malperfusion (FVM).
Chi-square and t-tests were used to compare outcomes across groups. Adjusted odds ratio were calculated using logistic regression. Statistical significance set at P <.05, two-tailed.
Main results and the role of chance
No patient had a history of chronic hypertension/smoking. Group 1 Patients conceived by DO, with FET and freshET were comparable with regards to age (34.1 vs 36.4years, P=.07),BMI(26.7 vs 27.1 kg/m2,P=.6),nulliparity(81%vs82%,P=.9) HDP(25%vs29.4%,P=0.69),birth-weight(2.48 vs 2.47kg,P=.93) LBW(31.3%vs41.2%,P=.41)respectively
PTD was significantly less in donor FET versus donor freshET (6.3%vs47.1%P=.0002) Placental weight and cord mal-insertions were comparable for FET vs freshET (466 vs 486gms P=.03 12.5%vs23.5% P=.25)respectively. Amongst the placental histopathology lesions, immune/ idiopathic-inflammatory lesions were significantly more in the FET vs freshET group (37.5% vs 11.8%,P=.02)The other lesions were comparable infectious-inflammatory(6.3%vs17.6%,P=.16), MVM(75%vs58.8%, P=.16),FVM(18.8%vs17.6%,P=.9)
Group 2 Patients conceived by DO compared to AO by FET were significantly older and had a higher BMI (34.1vs31.7years,P=.02 ,26.7vs25.5 kg/m2,P=.002) respectively.
Nulliparity was comparable(81%vs92%,P=.15) Birth weight was significantly less in DO vs AO(2.4vs2.7kg,P=.02) HDP and LBW were significantly more in DO vs AO(25%vs8% ,P=.03, 31.3%vs 8%,P=.007),respectively. PTD was comparable(6.3%vs8.0%,P=.77). Placental weight was significantly less in DO vs AO (466 vs 513gms,P=.03) cord mal-insertions were comparable(12.5% vs 24%,P=.2) The MVM lesions were significantly more in the DO group compared to AO(75% vs 40%,P=.002)
The difference remained after adjusting for age/BMI/HDP (AOR 4.31;95% CI 1.24–14.8;P=.02). The rest of placental lesions were comparable in DO vs AO, infectious-inflammatory lesions(6.3%vs16%,P=.19) immune/idiopathic-inflammatory lesions(37.5%vs28%,P=.37) FVM(18.8% vs 12%,P=.4)respectively.
Limitations, reasons for caution
These findings are based on a small number of patients. The results observed need to be confirmed using a larger study sample.
Wider implications of the findings: Placentas in pregnancies by embryo-vitrification, in a DO-model, had significantly more immune/idiopathic-inflammation, the cause/significance of this needs to be explored. Placentas in DO-pregnancies had significantly more MVM-lesions and increased risk of HDP, emphasizing the clinical/histopathological link of DO with HDP and the need for counselling/preventive strategies for HDP in DO-pregnancie.
Trial registration number
Not applicable
Dose–response relationships between maternal urinary cotinine and placental weight and ratio of placental weight to birth weight: The Japan Environment and Children's Study
