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FSH receptor N680S genotype-guided gonadotropin choice increases cumulative pregnancy and live birth rates after in vitro fertilization

Hjelmér, Ida LU ; Nilsson, Mathilda LU orcid ; Henic, Emir LU ; Jedrzejczak, Piotr ; Nenonen, Hannah LU ; Ozegowska, Katarzyna ; Giwercman, Aleksander LU ; Laczna Kitlinski, Margareta and Lundberg Giwercman, Yvonne LU (2025) In Frontiers in Endocrinology 16.
Abstract
Objective: This study aimed to compare cumulative [fresh and frozen embryo transfers from one ovarian stimulation (OS) cycle] pregnancy and live birth rates in women for whom the choice between recombinant FSH (rFSH) and urinary FSH (uFSH) for OS was linked to FSH receptor (FSHR) N680S genotype and compared these to non-genotyped controls.

Methods: To define the optimal combination of FSH type and FSHR genotype, 475 women were allocated to either the rFSH group or to the uFSH group for OS. The number of aspirated oocytes, cumulative pregnancy rates, and live birth rates in the first OS cycle were determined. Subsequently, their FSHR N680S (rs6166) variant was analyzed. Clinical data were backed up by in vitro experiments, in which... (More)
Objective: This study aimed to compare cumulative [fresh and frozen embryo transfers from one ovarian stimulation (OS) cycle] pregnancy and live birth rates in women for whom the choice between recombinant FSH (rFSH) and urinary FSH (uFSH) for OS was linked to FSH receptor (FSHR) N680S genotype and compared these to non-genotyped controls.

Methods: To define the optimal combination of FSH type and FSHR genotype, 475 women were allocated to either the rFSH group or to the uFSH group for OS. The number of aspirated oocytes, cumulative pregnancy rates, and live birth rates in the first OS cycle were determined. Subsequently, their FSHR N680S (rs6166) variant was analyzed. Clinical data were backed up by in vitro experiments, in which COS-1 cells were transfected with homozygous FSHR variants and stimulated with either uFSH or rFSH. cAMP was measured to evaluate receptor activity. Thereafter, a sub-cohort of 221 who received optimal FSH treatment in relation to their FSHR genotype was selected from the total cohort of 475 women. Cumulative pregnancy and live birth rates were compared between 991 non-genotyped controls and these 221 women. Binary logistic regression was used to explore the odds ratios (ORs) and 95% confidence intervals (CIs) for cumulative pregnancy and live birth rates in the first OS cycle among genotyped and optimally treated women, with the non-genotyped cohort set as the reference. Adjustment was made for age, body mass index, and method of fertilization.

Results: The combined clinical and in vitro data indicated that uFSH was the optimal choice for FSHR N680S S-allele carriers, whereas rFSH was the hormone of choice for asparagine (NN) subjects. The sub-cohort consisting of uFSH-treated S-carriers together with rFSH-treated NN-carriers had a significantly higher chance of pregnancy (51% vs. 40%; OR: 1.40, 95% CI 1.12-1.75, p=0.003) and live birth (40% vs. 29%; OR: 1.55, 95% CI 1.23-1.96, p<0.001) compared to non-genotyped women, in whom the choice of hormone was based on a standard clinical evaluation.

Conclusion: A significantly increased chance of pregnancy and live birth can be achieved by a genotype-guided approach. While the administration of uFSH should be the choice for S-carriers, rFSH is beneficial for NN-carrying women. (Less)
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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
FSHR, IVF, polymorphism, infertility, Gonadotropin, pregnancy, live birth
in
Frontiers in Endocrinology
volume
16
pages
10 pages
publisher
Frontiers Media S. A.
external identifiers
  • pmid:40433406
ISSN
1664-2392
DOI
10.3389/fendo.2025.1576090
language
English
LU publication?
yes
id
fae95fa6-f6ad-4cbe-9a69-5c1dc765044d
date added to LUP
2025-05-28 09:29:55
date last changed
2025-05-29 03:00:07
@article{fae95fa6-f6ad-4cbe-9a69-5c1dc765044d,
  abstract     = {{Objective: This study aimed to compare cumulative [fresh and frozen embryo transfers from one ovarian stimulation (OS) cycle] pregnancy and live birth rates in women for whom the choice between recombinant FSH (rFSH) and urinary FSH (uFSH) for OS was linked to FSH receptor (FSHR) N680S genotype and compared these to non-genotyped controls.<br/><br/>Methods: To define the optimal combination of FSH type and FSHR genotype, 475 women were allocated to either the rFSH group or to the uFSH group for OS. The number of aspirated oocytes, cumulative pregnancy rates, and live birth rates in the first OS cycle were determined. Subsequently, their FSHR N680S (rs6166) variant was analyzed. Clinical data were backed up by in vitro experiments, in which COS-1 cells were transfected with homozygous FSHR variants and stimulated with either uFSH or rFSH. cAMP was measured to evaluate receptor activity. Thereafter, a sub-cohort of 221 who received optimal FSH treatment in relation to their FSHR genotype was selected from the total cohort of 475 women. Cumulative pregnancy and live birth rates were compared between 991 non-genotyped controls and these 221 women. Binary logistic regression was used to explore the odds ratios (ORs) and 95% confidence intervals (CIs) for cumulative pregnancy and live birth rates in the first OS cycle among genotyped and optimally treated women, with the non-genotyped cohort set as the reference. Adjustment was made for age, body mass index, and method of fertilization.<br/><br/>Results: The combined clinical and in vitro data indicated that uFSH was the optimal choice for FSHR N680S S-allele carriers, whereas rFSH was the hormone of choice for asparagine (NN) subjects. The sub-cohort consisting of uFSH-treated S-carriers together with rFSH-treated NN-carriers had a significantly higher chance of pregnancy (51% vs. 40%; OR: 1.40, 95% CI 1.12-1.75, p=0.003) and live birth (40% vs. 29%; OR: 1.55, 95% CI 1.23-1.96, p&lt;0.001) compared to non-genotyped women, in whom the choice of hormone was based on a standard clinical evaluation.<br/><br/>Conclusion: A significantly increased chance of pregnancy and live birth can be achieved by a genotype-guided approach. While the administration of uFSH should be the choice for S-carriers, rFSH is beneficial for NN-carrying women.}},
  author       = {{Hjelmér, Ida and Nilsson, Mathilda and Henic, Emir and Jedrzejczak, Piotr and Nenonen, Hannah and Ozegowska, Katarzyna and Giwercman, Aleksander and Laczna Kitlinski, Margareta and Lundberg Giwercman, Yvonne}},
  issn         = {{1664-2392}},
  keywords     = {{FSHR; IVF; polymorphism; infertility; Gonadotropin; pregnancy; live birth}},
  language     = {{eng}},
  month        = {{05}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Endocrinology}},
  title        = {{FSH receptor N680S genotype-guided gonadotropin choice increases cumulative pregnancy and live birth rates after in vitro fertilization}},
  url          = {{http://dx.doi.org/10.3389/fendo.2025.1576090}},
  doi          = {{10.3389/fendo.2025.1576090}},
  volume       = {{16}},
  year         = {{2025}},
}