A C TA Obstetricia et Gynecologica
AOGS M A I N R E SE A RC H A R TI C LE
Maternal age and serum concentration of human chorionic gonadotropin in early pregnancy CAMILLA HAAVALDSEN1,2, PETER FEDORCSAK3, TOM TANBO2,3 & ANNE ESKILD1,2,4 1
Department of Gynecology and Obstetrics, Akershus University Hospital, Lørenskog, 2Institute of Clinical Medicine, University of Oslo, 3Section for Reproductive Medicine, Department of Gynecology, Oslo University Hospital, Rikshospitalet, and 4Division of Mental Health, Norwegian Institute of Public Health, Oslo, Norway
Key words Human chorionic gonadotropin, in vitro fertilization, maternal age, pregnancy, reproductive endocrinology Correspondence Camilla Haavaldsen, Department of Gynecology and Obstetrics, Akershus University Hospital, 1478 Lørenskog, Norway. E-mail: [email protected] Conflict of interest The authors have stated explicitly that there are no conflicts of interest in connection with this article. Please cite this article as: Haavaldsen C, Fedorcsak P, Tanbo T, Eskild A. Maternal age and serum concentration of human chorionic gonadotropin in early pregnancy. Acta Obstet Gynecol Scand 2014; 93: 1290–1294. Received: 6 March 2014 Accepted: 4 August 2014 DOI: 10.1111/aogs.12471
Abstract Objective. To study whether maternal age is associated with serum concentration of human chorionic gonadotropin in early pregnancy. Design. Crosssectional study. Setting. Oslo University Hospital in Oslo, Norway. Population. All vital pregnancies in gestational week 8 conceived by in vitro fertilization between February 1996 and February 2013 (n = 4472). Methods. Serum concentrations of human chorionic gonadotropin were measured on day 12 after embryo transfer/day 16 following ovulation induction. Trends in geometric means of human chorionic gonadotropin concentrations by maternal age group were tested by linear regression analysis. We also studied the association of maternal age (years) with log-transformed human chorionic gonadotropin concentrations, and adjustments were made for number of embryos transferred, method of in vitro fertilization and year (period) of embryo transfer. Main outcome measure. Serum concentration of human chorionic gonadotropin. Results. Geometric mean concentrations of human chorionic gonadotropin decreased with increasing maternal age (p = 0.024, test for trend by weighted linear regression). Also, we estimated a significant negative association of maternal age with log-transformed human chorionic gonadotropin concentrations (adjusted regression coefficient 0.011, standard error 0.003, p < 0.001). Conclusions. Serum concentrations of human chorionic gonadotropin in very early pregnancy decreased with maternal age. Since human chorionic gonadotropin is synthesized in trophoblast cells only, the lower human chorionic gonadotropin concentrations in women of advanced age may reflect functional impairment or delayed proliferation of trophoblast cells in early pregnancy in these women. CI, confidence interval; hCG, human chorionic gonadotropin; ICSI, intra-cytoplasmic sperm injection; IVF, in vitro fertilization.
Abbreviations:
In pregnancy, human chorionic gonadotropin (hCG) is produced by trophoblast cells in the placenta. hCG
Introduction Postponing childbearing into the late reproductive period is becoming increasingly common. Pregnancies of older mothers have an increased risk for adverse pregnancy outcomes, such as miscarriage (1), preeclampsia (2) and fetal death (3). However, the reasons for the increase in risks remain insufficiently understood.
1290
Key Message Serum concentrations of hCG in very early pregnancy decrease with maternal age.
ª 2014 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 93 (2014) 1290–1294
C. Haavaldsen et al.
promotes the maintenance of the corpus luteum in early pregnancy, which produces and secretes progesterone. hCG is also known as an angiogenic factor, and it stimulates uterine and placental development (4–6). There is a large inter-individual variation in maternal serum concentrations of hCG in early pregnancy (7). Knowledge of the underlying mechanisms of such variation may increase our understanding of the role of hCG in pregnancy. Older women have an increased risk for adverse pregnancy outcome. Low concentrations of hCG have been associated with increased risk for miscarriage (8,9) and preeclampsia (10). However, it is not known whether older women have lower serum concentrations of hCG in early pregnancy compared with younger women. We studied the association of maternal age with hCG concentrations in 4472 pregnancies conceived by in vitro fertilization (IVF) at a Norwegian university hospital.
Material and methods In this cross-sectional study, pregnancies after IVF at the Oslo University Hospital, Rikshospitalet, in Oslo, Norway, between February 1996 and February 2013 constituted the study population. We included all pregnancies that had been confirmed as vital by ultrasonographic examination in gestational week 8 (6 weeks after embryo transfer). We included all pregnancies after transfer of fresh embryos from IVF with or without intra-cytoplasmic sperm injection (ICSI), or after transfer of frozen/thawed embryos (n = 5326). All oocytes used for treatment were autologous, and all embryos were transferred on day 2–3 after egg retrieval at the two-cell to eight-cell stage. In 4552 women, serum concentrations of hCG were measured in the morning of day 12 after embryo transfer (frozen/ thawed) or day 16 after ovulation induction with exogenous hCG (fresh embryos) (Figure 1) (11). In 77 pregnancies, three embryos had been transferred. Since three embryos had been transferred to highly selected women with repeated treatment failure or very poor embryo quality, we decided to exclude these pregnancies. We also excluded the three pregnancies with outlying values of hCG concentrations (≥1000 IU/L) (7,8,12). Thus, a total of 4472 pregnancies could be included. Human chorionic gonadotropin was quantified at the Department of Biochemistry, Oslo University Hospital, Rikshospitalet. An electrochemiluminescence immunoassay method was used (Elecsys; Roche, Basel, Switzerland), and intact hCG and free hCG chains were measured with a detection limit of 0.5 mIU/mL. Quality control at the hospital has shown low within-series variation (coefficient of variation,
AOGS M A I N R E SE A RC H A R TI C LE
Maternal age and serum concentration of human chorionic gonadotropin in early pregnancy CAMILLA HAAVALDSEN1,2, PETER FEDORCSAK3, TOM TANBO2,3 & ANNE ESKILD1,2,4 1
Department of Gynecology and Obstetrics, Akershus University Hospital, Lørenskog, 2Institute of Clinical Medicine, University of Oslo, 3Section for Reproductive Medicine, Department of Gynecology, Oslo University Hospital, Rikshospitalet, and 4Division of Mental Health, Norwegian Institute of Public Health, Oslo, Norway
Key words Human chorionic gonadotropin, in vitro fertilization, maternal age, pregnancy, reproductive endocrinology Correspondence Camilla Haavaldsen, Department of Gynecology and Obstetrics, Akershus University Hospital, 1478 Lørenskog, Norway. E-mail: [email protected] Conflict of interest The authors have stated explicitly that there are no conflicts of interest in connection with this article. Please cite this article as: Haavaldsen C, Fedorcsak P, Tanbo T, Eskild A. Maternal age and serum concentration of human chorionic gonadotropin in early pregnancy. Acta Obstet Gynecol Scand 2014; 93: 1290–1294. Received: 6 March 2014 Accepted: 4 August 2014 DOI: 10.1111/aogs.12471
Abstract Objective. To study whether maternal age is associated with serum concentration of human chorionic gonadotropin in early pregnancy. Design. Crosssectional study. Setting. Oslo University Hospital in Oslo, Norway. Population. All vital pregnancies in gestational week 8 conceived by in vitro fertilization between February 1996 and February 2013 (n = 4472). Methods. Serum concentrations of human chorionic gonadotropin were measured on day 12 after embryo transfer/day 16 following ovulation induction. Trends in geometric means of human chorionic gonadotropin concentrations by maternal age group were tested by linear regression analysis. We also studied the association of maternal age (years) with log-transformed human chorionic gonadotropin concentrations, and adjustments were made for number of embryos transferred, method of in vitro fertilization and year (period) of embryo transfer. Main outcome measure. Serum concentration of human chorionic gonadotropin. Results. Geometric mean concentrations of human chorionic gonadotropin decreased with increasing maternal age (p = 0.024, test for trend by weighted linear regression). Also, we estimated a significant negative association of maternal age with log-transformed human chorionic gonadotropin concentrations (adjusted regression coefficient 0.011, standard error 0.003, p < 0.001). Conclusions. Serum concentrations of human chorionic gonadotropin in very early pregnancy decreased with maternal age. Since human chorionic gonadotropin is synthesized in trophoblast cells only, the lower human chorionic gonadotropin concentrations in women of advanced age may reflect functional impairment or delayed proliferation of trophoblast cells in early pregnancy in these women. CI, confidence interval; hCG, human chorionic gonadotropin; ICSI, intra-cytoplasmic sperm injection; IVF, in vitro fertilization.
Abbreviations:
In pregnancy, human chorionic gonadotropin (hCG) is produced by trophoblast cells in the placenta. hCG
Introduction Postponing childbearing into the late reproductive period is becoming increasingly common. Pregnancies of older mothers have an increased risk for adverse pregnancy outcomes, such as miscarriage (1), preeclampsia (2) and fetal death (3). However, the reasons for the increase in risks remain insufficiently understood.
1290
Key Message Serum concentrations of hCG in very early pregnancy decrease with maternal age.
ª 2014 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 93 (2014) 1290–1294
C. Haavaldsen et al.
promotes the maintenance of the corpus luteum in early pregnancy, which produces and secretes progesterone. hCG is also known as an angiogenic factor, and it stimulates uterine and placental development (4–6). There is a large inter-individual variation in maternal serum concentrations of hCG in early pregnancy (7). Knowledge of the underlying mechanisms of such variation may increase our understanding of the role of hCG in pregnancy. Older women have an increased risk for adverse pregnancy outcome. Low concentrations of hCG have been associated with increased risk for miscarriage (8,9) and preeclampsia (10). However, it is not known whether older women have lower serum concentrations of hCG in early pregnancy compared with younger women. We studied the association of maternal age with hCG concentrations in 4472 pregnancies conceived by in vitro fertilization (IVF) at a Norwegian university hospital.
Material and methods In this cross-sectional study, pregnancies after IVF at the Oslo University Hospital, Rikshospitalet, in Oslo, Norway, between February 1996 and February 2013 constituted the study population. We included all pregnancies that had been confirmed as vital by ultrasonographic examination in gestational week 8 (6 weeks after embryo transfer). We included all pregnancies after transfer of fresh embryos from IVF with or without intra-cytoplasmic sperm injection (ICSI), or after transfer of frozen/thawed embryos (n = 5326). All oocytes used for treatment were autologous, and all embryos were transferred on day 2–3 after egg retrieval at the two-cell to eight-cell stage. In 4552 women, serum concentrations of hCG were measured in the morning of day 12 after embryo transfer (frozen/ thawed) or day 16 after ovulation induction with exogenous hCG (fresh embryos) (Figure 1) (11). In 77 pregnancies, three embryos had been transferred. Since three embryos had been transferred to highly selected women with repeated treatment failure or very poor embryo quality, we decided to exclude these pregnancies. We also excluded the three pregnancies with outlying values of hCG concentrations (≥1000 IU/L) (7,8,12). Thus, a total of 4472 pregnancies could be included. Human chorionic gonadotropin was quantified at the Department of Biochemistry, Oslo University Hospital, Rikshospitalet. An electrochemiluminescence immunoassay method was used (Elecsys; Roche, Basel, Switzerland), and intact hCG and free hCG chains were measured with a detection limit of 0.5 mIU/mL. Quality control at the hospital has shown low within-series variation (coefficient of variation,
