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Doubtful association between progesterone therapy and fetal nuchal translucency
Accepted Manuscript Doubtful association between progesterone therapy and fetal nuchal translucency Vicente Serra, MD, Nicolás Garrido, PhD, José Bellver, MD PII:
S0002-9378(15)00511-6
DOI:
10.1016/j.ajog.2015.05.035
Reference:
YMOB 10418
To appear in:
American Journal of Obstetrics and Gynecology
Received Date: 18 April 2015 Accepted Date: 19 May 2015
Please cite this article as: Serra V, Garrido N, Bellver J, Doubtful association between progesterone therapy and fetal nuchal translucency, American Journal of Obstetrics and Gynecology (2015), doi: 10.1016/j.ajog.2015.05.035. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Doubtful association between progesterone therapy and fetal nuchal translucency Vicente Serraa,b, MD; Nicolás Garridoa, PhD; & José Bellvera,b, MD. a
Instituto Valenciano de Infertilidad; and bDepartamento de Pediatría, Obstetricia y Ginecología. Facultad de Medicina. Universidad de Valencia. Valencia, Spain.
RI PT
Dear Editor of the AJOG:
M AN U
SC
We read with great interest the paper on the potential effect of progesterone therapy during the first trimester on the fetal nuchal translucency (NT) thickness1. The authors advocate that exogenous progesterone increases NT. However, we feel that this assumption is not supported by their data. First, the authors show only a very mild NT increase of only 0.04 multiples of the median (MoM) which, although minimally statistically significant (p<0.05), it is clearly clinically not relevant. In the low-risk group, the difference in the NT was even lower (0.02 MoM). Second, comparisons by week of gestation only showed NT differences at 11 weeks (p<0.02) but not at 12 and 13 weeks. This is important as most of the screenings are now performed at 12-13 weeks to check also the early fetal anatomy. Third, their results are based on a mixture of different progestogens, administered by different routes and at different doses, making comparisons difficult to interpret. And fourth, most of the progesterone-treated pregnancies (77.7%) had a threatened miscarriage and, to rule out a potential influence of such bleedings on fetal hemodynamics and NT, the authors should have also performed a sub-analysis omitting this group, or compared it to another group of untreated threatened miscarriage.
TE D
There is extensive evidence among studies in pregnancies achieved by assisted conceptions2-3 which demonstrate, indirectly, the lack of influence of progesterone on NT. Our own data2 show the lack of even a trend of any effect of micronized natural progesterone on NT (P=NS), despite including a subgroup with a maximum dose of natural progesterone (Table 1).
AC C
EP
Multiple pregnancies have a higher overall placental production of progesterone, providing a natural model to study this issue. No differences in NT values are found between multiple and singleton pregnancies4. This may also be used as an additional proof of the lack of influence of progesterone on NT.
1.
Giorlandino C, Cignini P, Padula F, et al. Effects of exogenous progesterone on fetal nuchal translucency: an observational prospective study. Am J Obstet Gynecol 2015;212:335.e1-7.
2.
Bellver J, Casanova C, Garrido N, Lara C, Remohi J, Pellicer A, Serra V. Additive effect of factors related to assisted conception on the reduction of maternal serum pregnancy-associated plasma protein A concentrations and the increased false-positive rates in first-trimester Down syndrome screening. Fertil Steril. 2013;100:1314-20.
3.
Matilainen M, Peuhkurinen S, Laitinen P, Jarvela I, Morin-Papunen L, Ryynanen M. In combined first-trimester Down syndrome screening, the false-positive rate is not higher in pregnancies conceived after assisted reproduction compared with spontaneous pregnancies. Fertil Steril 2011;95:378–81.
ACCEPTED MANUSCRIPT 4.
Mashiach R, Orr-Urtreger A, Yaron Y. A comparison between maternal serum free beta-human chorionic gonadotrophin and pregnancy-associated plasma protein A levels in first-trimester twin and singleton pregnancies. Fetal Diagn Ther. 2004;19:174-7.
Table 1.- NT measurements according to the mode of conception and average dose of natural progesterone administered2 Average daily dose of vaginal micronized natural progesterone until the 12th week
N
0
2011
Intrauterine insemination
200 mg*
350
IVF/ICSI with own oocytes
400 mg¥
IVF/ICSI with ovum donation
800 mg¥
RI PT 0.98 (0.96-0.99)
SC
0.97 (0.94-1.0)
1086
0.98 (0.96-1.0)
606
0.96 (0.94-0.98)
M AN U
Natural conception
NT MoM Mean (95% CI)
TE D
From the day of insemination* or day 1 of embryo development¥
AC C
EP
Total = 390 words (text+table) / 4 references / 3 authors / 1 Table
S0002-9378(15)00511-6
DOI:
10.1016/j.ajog.2015.05.035
Reference:
YMOB 10418
To appear in:
American Journal of Obstetrics and Gynecology
Received Date: 18 April 2015 Accepted Date: 19 May 2015
Please cite this article as: Serra V, Garrido N, Bellver J, Doubtful association between progesterone therapy and fetal nuchal translucency, American Journal of Obstetrics and Gynecology (2015), doi: 10.1016/j.ajog.2015.05.035. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Doubtful association between progesterone therapy and fetal nuchal translucency Vicente Serraa,b, MD; Nicolás Garridoa, PhD; & José Bellvera,b, MD. a
Instituto Valenciano de Infertilidad; and bDepartamento de Pediatría, Obstetricia y Ginecología. Facultad de Medicina. Universidad de Valencia. Valencia, Spain.
RI PT
Dear Editor of the AJOG:
M AN U
SC
We read with great interest the paper on the potential effect of progesterone therapy during the first trimester on the fetal nuchal translucency (NT) thickness1. The authors advocate that exogenous progesterone increases NT. However, we feel that this assumption is not supported by their data. First, the authors show only a very mild NT increase of only 0.04 multiples of the median (MoM) which, although minimally statistically significant (p<0.05), it is clearly clinically not relevant. In the low-risk group, the difference in the NT was even lower (0.02 MoM). Second, comparisons by week of gestation only showed NT differences at 11 weeks (p<0.02) but not at 12 and 13 weeks. This is important as most of the screenings are now performed at 12-13 weeks to check also the early fetal anatomy. Third, their results are based on a mixture of different progestogens, administered by different routes and at different doses, making comparisons difficult to interpret. And fourth, most of the progesterone-treated pregnancies (77.7%) had a threatened miscarriage and, to rule out a potential influence of such bleedings on fetal hemodynamics and NT, the authors should have also performed a sub-analysis omitting this group, or compared it to another group of untreated threatened miscarriage.
TE D
There is extensive evidence among studies in pregnancies achieved by assisted conceptions2-3 which demonstrate, indirectly, the lack of influence of progesterone on NT. Our own data2 show the lack of even a trend of any effect of micronized natural progesterone on NT (P=NS), despite including a subgroup with a maximum dose of natural progesterone (Table 1).
AC C
EP
Multiple pregnancies have a higher overall placental production of progesterone, providing a natural model to study this issue. No differences in NT values are found between multiple and singleton pregnancies4. This may also be used as an additional proof of the lack of influence of progesterone on NT.
1.
Giorlandino C, Cignini P, Padula F, et al. Effects of exogenous progesterone on fetal nuchal translucency: an observational prospective study. Am J Obstet Gynecol 2015;212:335.e1-7.
2.
Bellver J, Casanova C, Garrido N, Lara C, Remohi J, Pellicer A, Serra V. Additive effect of factors related to assisted conception on the reduction of maternal serum pregnancy-associated plasma protein A concentrations and the increased false-positive rates in first-trimester Down syndrome screening. Fertil Steril. 2013;100:1314-20.
3.
Matilainen M, Peuhkurinen S, Laitinen P, Jarvela I, Morin-Papunen L, Ryynanen M. In combined first-trimester Down syndrome screening, the false-positive rate is not higher in pregnancies conceived after assisted reproduction compared with spontaneous pregnancies. Fertil Steril 2011;95:378–81.
ACCEPTED MANUSCRIPT 4.
Mashiach R, Orr-Urtreger A, Yaron Y. A comparison between maternal serum free beta-human chorionic gonadotrophin and pregnancy-associated plasma protein A levels in first-trimester twin and singleton pregnancies. Fetal Diagn Ther. 2004;19:174-7.
Table 1.- NT measurements according to the mode of conception and average dose of natural progesterone administered2 Average daily dose of vaginal micronized natural progesterone until the 12th week
N
0
2011
Intrauterine insemination
200 mg*
350
IVF/ICSI with own oocytes
400 mg¥
IVF/ICSI with ovum donation
800 mg¥
RI PT 0.98 (0.96-0.99)
SC
0.97 (0.94-1.0)
1086
0.98 (0.96-1.0)
606
0.96 (0.94-0.98)
M AN U
Natural conception
NT MoM Mean (95% CI)
TE D
From the day of insemination* or day 1 of embryo development¥
AC C
EP
Total = 390 words (text+table) / 4 references / 3 authors / 1 Table