title: Controlled ovarian hyperstimulation leads to high progesterone and estradiol levels during early pregnancy.
abstract: OBJECTIVE
  Are there differences in estrogen and progesterone secretion in singleton pregnancies, up to Week 11, between spontaneous pregnancies, after controlled ovarian hyperstimulation and fresh embryo transfer (COH + ET) and after frozen embryo transfer in a spontaneous cycle (FET)?
  
  
  CONCLUSIONS
  Serum progesterone and estradiol (E2) concentrations after COH + ET were higher in early pregnancy, lasting up to Week 7-8, than FET and spontaneous pregnancies, while hormone levels after FET did not differ from spontaneous pregnancies.
  
  
  BACKGROUND
  The risk of adverse perinatal outcomes after COH + ET seems to be increased when compared with spontaneous pregnancies. One of the reasons suggested for this is related to ovarian hyperstimulation.
  
  
  METHODS
  This was a prospective cohort study consisting of three different groups of pregnant women which were followed-up weekly until Week 11 of their pregnancies. The spontaneous pregnancy group consisted of 41 women, the COH + ET group consisted of 39 and the FET group consisted of 30 women.
  
  
  METHODS
  Women in the control group with spontaneous conception were recruited from local prenatal clinics. Women in the COH + ET and FET groups were recruited from the Reproductive Unit of Oulu University Hospital. At each visit, a three-dimensional ultrasonography was performed to examine the ovarian volumes and vascularization. A blood sample was drawn to analyse progesterone and E2 levels. The pregnancy outcome was included in the analysis.
  
  
  RESULTS
  At pregnancy Week 5, the serum progesterone levels were higher after the COH + ET (median 312, inter-quartile range 183-480 nmol/l), when compared with the spontaneous (63, 52-80 nmol/l; P < 0.001) and FET (74, 48-96 nmol/l; P < 0.001) pregnancies. At Week 11, the P (189, 124-260 nmol/l) was still higher in the COH + ET group (FET 101, 78-120 nmol/l, P < 0.001; spontaneous 115, 80-139 nmol/l, P < 0.01) than the other two groups. The E2 levels at Week 5 were also significantly higher after COH + ET (4.1, 2.2-6.6 nmol/l) than in the spontaneous pregnancies (1.1, 0.7-1.6 nmol/l, P < 0.001) or after FET (0.7, 0.6-0.9 nmol/l, P < 0.001). The volume of the ovaries and the intraovarian vasculature in the COH + ET group were significantly higher when compared with the other two groups (P < 0.001). The birthweight was negatively correlated with the serum P (R -0.340, P < 0.01) and E2 (R= -0.275, P < 0.05) in pregnancy Weeks 5-8. In the multivariate analysis evaluating the factors affecting birthweight of the newborn, the significant factors were the length of gestation, maternal height and progesterone or E2 secretion during Weeks 5-8.
  
  
  CONCLUSIONS
  Because of the low number of patients in this study, larger cohort studies are required to confirm the findings.
  
  
  CONCLUSIONS
  The findings here indicate that COH-induced increased luteal activity should be evaluated by measuring steroid levels or the ovarian size or vascularity, rather than number of oocytes retrieved. If unphysiologically high steroid activity during pregnancy after COH contributes to the risk of adverse perinatal outcomes after fresh embryo transfer, milder stimulation protocols or even freezing of all of the embryos should be considered.
  
  
  BACKGROUND
  This study was supported by a research grant from the Academy of Finland. The authors declare no conflicts of interest.
authors.affiliation: Department of Obstetrics and Gynaecology, Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland ilkka.jarvela@oulu.fi.
authors.forename: Ilkka Y
authors.initials: IY
authors.lastname: Järvelä
authors.affiliation: Department of Obstetrics and Gynaecology, Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland.
authors.forename: Sari
authors.initials: S
authors.lastname: Pelkonen
authors.affiliation: Department of Obstetrics and Gynaecology, Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland.
authors.forename: Outi
authors.initials: O
authors.lastname: Uimari
authors.affiliation: Department of Obstetrics and Gynaecology, Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland.
authors.forename: Kaarin
authors.initials: K
authors.lastname: Mäkikallio
authors.affiliation: Department of Clinical Chemistry, Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland.
authors.forename: Katri
authors.initials: K
authors.lastname: Puukka
authors.affiliation: Department of Clinical Chemistry, Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland.
authors.forename: Aimo
authors.initials: A
authors.lastname: Ruokonen
authors.affiliation: Department of Obstetrics and Gynaecology, Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland.
authors.forename: Aydin
authors.initials: A
authors.lastname: Tekay
authors.affiliation: Department of Obstetrics and Gynaecology, Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland.
authors.forename: Hannu
authors.initials: H
authors.lastname: Martikainen
mesh_terms: D000328:Adult; D001724:Birth Weight; D004958:Estradiol / Q000097:blood*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D010053:Ovary / Q000000981:diagnostic imaging; D010062:Ovulation Induction / Q000379:methods*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011261:Pregnancy Trimester, First / Q000097:blood*; D011374:Progesterone / Q000097:blood*; D011446:Prospective Studies; D014463:Ultrasonography; D055815:Young Adult
chemical_list: D011374:Progesterone; D004958:Estradiol
keywords: controlled ovarian hyperstimulation; luteal activity; luteoplacental shift; placenta; three-dimensional ultrasonography