Abstract
Study question
Does the presence of corpus luteum (CL) in in vitro fertilization (IVF) treatments affect maternal and fetal concentrations of hemopexin and α1-microglobulin in preeclampsia?
Summary answer
Decreased hemopexin and increased α1-microglobulin levels in maternal and fetal blood in IVF pregnancies with absence of CL particularly in pregnancies complicated by preeclampsia.
What is known already:
Pregnancies after frozen embryo transfer (FET) in programmed cycles have higher rates of hypertensive disorders of pregnancy, suggesting a link between the absence of CL in programmed cycles and adverse maternal outcomes.Cardiovascular function is impaired early in pregnancy in women conceiving by IVF treatments in the absence of CL.Plasma relaxin–2, a potent vasodilator and stimulus of decidualization, has been reported to be undetectable in a non-CL cohort, but markedly elevated in a multiple-CL cohort through pregnancy.Hemopexin and α1-microglobulin act as scavengers that eliminate free heme-groups responsible for hemoglobin-induced oxidative stress known to contribute to preeclampsia development.
Study design, size, duration
A case-control study of 160 singleton pregnancies recruited from 2016 to 2020, including 54 spontaneous pregnancies from fertile couples, 50 conceived by IVF following fresh embryo transfer (ET) and FET in natural cycle (presence of CL) and 56 IVF after fresh oocyte-donation or FET in programmed cycles (absence of CL). Pregnancies were subclassified according to the presence of preeclampsia in uncomplicated, preeclampsia and severe preeclampsia cases.
Participants/materials, setting, methods
IVF pregnancies were recruited from a single Assisted Reproduction Center, ensuring homogeneity in IVF stimulation protocols, endometrial preparation, laboratory procedures and embryo culture conditions. Spontaneous pregnancies from fertile couples were randomly selected from our general population and matched to IVF by gestational age at birth. Hemopexin and α1-microglobulin concentrations were measured by ELISA in maternal and cord plasma collected at delivery. All comparisons were adjusted for age, ethnicity, prematurity, birthweight centile, oocyte-donation and FET cycles.
Main results and the role of chance
Parental ethnicity, body mass index, exposure to aspirin and corticoids during pregnancy, mean gestational age at birth and birthweight were similar in all study groups. While maternal hemopexin levels were lower in treatments without CL, the IVF group with one or several CL showed significantly increased hemopexin concentrations, both in uncomplicated and preeclampsia cases (uncomplicated: spontaneous conceptions median 1520 ug/ml [interquartile range 1054–1746], IVF with CL 1554 [1315–1778], IVF without CL 1401 [1130–1750]; Preeclampsia: spontaneous conceptions 1362 [1121–1667], IVF with CL 1372 [403–2558], IVF without CL 1215 [971–1498]). Maternal α1-microglobulin was significantly higher in the absence of CL in severe preeclamptic cases as compared to spontaneous pregnancies and IVF with CL (spontaneous conceptions median 23 ug/ml [interquantile range 20–24], IVF with CL 24 [24–26], IVF without CL 26 [25–28]).
The cord blood profiles were identical to the maternal for both biomarkers.
Overall, and in line with previous studies, preeclamptic pregnancies independently of the mode of conception, showed decreased concentrations of hemopexin and increased concentrations of α1-microglobulin both in maternal and fetal plasma, with more pronounced changes in severe preeclampsia cases.
Limitations, reasons for caution
Infertility factors contribution to the outcome cannot be unraveled from the assisted reproductive technologies procedure itself as we have only included spontaneous pregnancies from fertile couples.
Adjustments for oocyte-donation and FET modalities were performed due to the higher proportion of these features in the ET in programmed cycles group.
Wider implications of the findings: These findings acknowledge physiological differences between pregnancies following ET in stimulated and natural versus programmed cycles, supporting the hypothesis that the CL activity could influence perinatal results.
This approach to perinatal outcomes in IVF patients could lead to changes in ET protocols in order to develop a CL if possible.
Trial registration number
Not applicable
Cleavage Stage versus Blastocyst Stage Embryo Transfer in Oocyte Donation Cycles
