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Original article 451

Significance of a common single nucleotide polymorphism in
exon 10 of the follicle-stimulating hormone (FSH) receptor
gene for the ovarian response to FSH: a pharmacogenetic
approach to controlled ovarian hyperstimulation
Hermann M. Behrea, Robert R. Grebc, Andrea Mempelc, Barbara Sonntagc,
Ludwig Kieselc, Petra Kaltwaßerb, Ewald Seligerb, Friedrich Ro¨pkeb,
Jo¨rg Gromolld, Eberhard Nieschlagd and Manuela Simonid
The p.N680S sequence variation of the follicle-stimulating
hormone (FSH) receptor gene was previously shown to
influence the ovarian response to FSH in normo-ovulatory
women undergoing controlled ovarian hyperstimulation. In
this prospective, randomized, controlled study, we tested
whether the same daily dose of FSH results in lower levels
of oestradiol in women homozygous for the p.N680S
sequence variation, and whether the difference can be
overcome by higher FSH doses. Women undergoing
controlled ovarian hyperstimulation for in vitro fertilization
or intracytoplasmic sperm injection and homozygous for
the wild-type or for the p.N680S FSH receptor were
randomly assigned to group I (Ser/Ser, n = 24), receiving
an FSH dose of 150 U/day, or group II (Ser/Ser, n = 25),
receiving an FSH dose of 225 U/day. In group III (Asn/Asn,
n = 44), the FSH dose was 150 U/day. Age and basal FSH
levels were not different between groups. At ovulation
induction, total FSH doses were comparable in group I
(1631 ± 96 U) and group III (1640 ± 57 U) but significantly
higher in group II (2421 ± 112 U) (P < 0.001). Peak oestradiol levels on the day of human chorionic gonadotrophin
(hCG) administration were significantly lower in group I
(5680 ± 675 pmol/l) compared to group III
(8679 ± 804 pmol/l) (P = 0.028). Increasing the FSH dose
from 150 to 225 U/day overcame the lower oestradiol

Introduction
Follicle-stimulating hormone (FSH) stimulates growth
and maturation of antral follicles and oestradiol production by granulosa cells and is widely used in assisted
reproduction. Assisted reproduction techniques (ART)
are indicated both for female and for male infertility and
require controlled ovarian hyperstimulation (COH) with
FSH to achieve maturation of multiple ovarian follicles
and oocytes, accompanied by high serum oestradiol levels.
It has long been known that the outcome of COH is
unpredictably variable between patients and the narrow
window between insufficient ovarian response and
development of a life-threatening ovarian hyperstimulation syndrome (OHSS) is a serious problem in individual
patients. As a result, although several ovarian stimulation
protocols have been developed in the last decades [1],
the FSH dosage for the individual patient is often chosen

response in women with Ser/Ser (group II,
7804 ± 983 pmol/l). In women undergoing controlled ovarian hyperstimulation, the p.N680S sequence variation
results in lower oestradiol levels following FSH stimulation.
This lower FSH receptor sensitivity can be overcome by
higher FSH doses. Pharmacogenetics and Genomics
c 2005 Lippincott Williams & Wilkins.
15:451–456
Pharmacogenetics and Genomics 2005, 15:451–456
Keywords: FSH, FSH receptor, ovarian stimulation, ovary,
sequence variation, SNP
a

Andrology Unit, Department of Urology, bDepartment of Obstetrics and
Reproductive Medicine, University Hospital, Halle, cDepartment of Obstetrics
and Gynaecology and dInstitute of Reproductive Medicine of the
University, University Hospital, Mu¨nster, Germany.

Sponsorship: This study was supported by a research grant of the German
Research Foundation (DFG project SI 526/1).

Correspondence and requests for reprints to Professor Manuela Simoni,
Institute of Reproductive Medicine, Domagkstrasse 11, D-48149 Mu¨nster,
Germany.
Tel: + 49 251 8356 444; fax: + 49 251 835 6093;
e-mail: manuela.simoni@ukmuenster.de

Received 28 February 2005 Accepted 18 April 2005

empirically and adjusted during the cycle. The identification of parameters predicting the ovarian response to
FSH stimulation is an important issue still to be solved in
reproductive endocrinology [2].
The effects of endogenous or exogenous FSH on the
ovary can be modulated by mutations or polymorphisms
of the FSH receptor gene [3,4]. Homozygous, inactivating mutations of the FSH receptor gene result in
hypergonadotropic ovarian dysgenesis with primary ovarian failure [5]. Screening for mutations revealed the
presence of two common single nucleotide polymorphisms (SNP) in the coding region of the FSH receptor
gene [5]. In a partly retrospective study, we hypothesized
a role for one of these SNPs in determining ovarian
response to FSH [6]. This functionally important SNP
(NCBI refSNP ID: rs6166) is located in exon 10 of the

c 2005 Lippincott Williams & Wilkins
1744-6872

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

indicating a lower ovarian sensitivity to FSH in vivo of the p. There was no restriction to a specific pharmaceutical preparation of FSH (urinary or recombinant) or GnRH analogues (agonist or antagonist) to reflect best daily practice therapy. where a G > A exchange at nucleotide position 2039 results in the occupation of codon 680 in the intracellular domain of the FSH receptor either by asparagine (Asn) or serine (Ser) [4]. whether the ovarian response to FSH in COH differs depending on the 2039G > A SNP. including ovarian cyst. all of Caucasian origin. IVF or ICSI therapy was performed according to standard protocols. which were randomized to be treated with a FSH dose of 150 U/day (group I) or 225 U/day (group II). Applied Biosystems. Premature luteinization was prevented by administration of gonadotrophin-releasing hormone (GnRH) analogues. (ii) they withdrew consent in the meantime for personal reasons. [919A > G. proof-of-principle study. in a prospective randomized controlled trial. (ii) normal menstrual cycle (24–35 days cycle duration). or (iii) they opted for the routine stimulation protocol. The remaining 113 homozygous women were not included because: (i) they were found to be ineligible upon rechecking for the inclusion criteria. As a parameter of FSH action. Patient inclusion criteria for the study were: (i) women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) therapy aged 18– 39 years. Group III (n = 44) included all women with the homozygous Asn/Asn genotype. ovarian endometriosis or polycystic ovary syndrome. Unauthorized reproduction of this article is prohibited. The study design was based on the hypothesis that the same FSH dose would be less efficient in stimulating oestradiol levels in Ser/Ser women compared to Asn/Asn women. II. Based on the results of our previous retrospective study [6]. potentially eligible patients from the ongoing assisted reproduction programs of the women’s hospitals of the Universities of Muenster and Halle were informed about the study and provided their informed consent to FSH receptor genotyping. Copyright © Lippincott Williams & Wilkins. Patients and methods Study design The study protocol was approved by the Ethics Committees of the Medical Faculties and State Medical Boards of the Universities of Muenster and Halle. and completed the study protocol as described below.N680S allele [6]. The three treatment groups (I. 2039G > A] (NCBI refSNP ID: rs6165). and that increasing the FSH dose in the Ser/Ser women would result in a response similar to that obtained in Asn/Asn women with a lower dose. 175 women were heterozygous Asn/ Ser and were not further considered. We analysed whether the same daily dose of FSH given for COH results in lower levels of oestradiol in women homozygous for the p. Randomization was performed by opening consecutively numbered sealed envelopes containing group assignments. independent of oestradiol serum concentration. These women were all treated with a FSH dose of 150 U/day. Germany. Germany). using the Taqman machine (ABI Prism 7000 sequence detection system. Darmstadt. A follicle size of at least 17 mm diameter. Exclusion of heterozygous women was decided to simplify the study design and improve the power of this relatively small-scale. the daily FSH dose was kept constant until ovulation induction and dose adjustment was not allowed. which were determined previously based upon random numbers. only women with FSH receptor genotype at codon 680 homozygous Asn/Asn or Ser/Ser were considered. Similar results were later obtained by other investigators [7–9]. confirmed their consent to participate in the study. were assigned to three treatment groups. In our partly retrospective. Consecutive.N680S allele compared to women homozygous for the wild-type FSH receptor. such as severe OHSS. and (v) serum FSH < 10 U/l on cycle day 3. as described previously [10]. (iii) no ovarian pathology. In addition. Ninety-three of 206 women with homozygous FSH receptor Asn/Asn or Ser/Ser. was the criterion for hCG administration for ovulation induction. The power analysis for the study and determination of the sample size was based on this primary end point. Vol 15 No 7 FSH receptor gene. pregnancy rates or adverse side-effects. Groups were assigned as follows. This multicentre interventional study was performed to test. In all three groups. Assessment of FSH receptor genotype The FSH receptor genotype at position 680 in exon 10 was analysed by the Taqman allelic discrimination assay. This polymorphism is mostly in linkage dysequilibrium with a SNP at nucleotide position 919. Both groups I (n = 24) and II (n = 25) included women with the homozygous Ser/Ser genotype. FSH receptor genotype was assessed in 381 consecutive women. we chose serum oestradiol levels on the day of ovulation induction by human chorionic gonadotrophin (hCG). resulting in two very common alleles almost equally distributed (55% versus 45%) in Caucasians [4]. non-randomized study. respectively. and whether a potential difference can be overcome by higher exogenous FSH. The study was not powered to detect differences in follicle or oocyte number. the primary endpoint parameter of the study was the serum concentration of oestradiol at the time of hCG injection for ovulation induction. Of those. . the amount of FSH needed for COH to achieve similar peak oestradiol levels was significantly lower in homozygous women with Asn/Asn at codon 680 of the FSH receptor gene compared to women with Ser/Ser or Asn/Ser.452 Pharmacogenetics and Genomics 2005. (iv) r 3 previous IVF or ICSI therapies. III) of the study were defined considering that COH starts usually with an FSH dose of 150 U/day.

ANOVA: P = 0. Unauthorized reproduction of this article is prohibited. whereas FSH dose was significantly higher in group II (2421 ± 112 U) (ANOVA: P < 0. P < 0. In the case of significant overall differences. P < 0.39) and basal FSH levels on cycle day 3 (group I: 5.. Fig.Pharmcogenetics of FSH treatment Behre et al. group III: 5. respectively. these data indicate similar follicular development dynamics in the three groups. Intra.1 ± 0. Because the only parameter for deciding when to discontinue FSH stimulation and proceed with ovulation induction was follicular diameter. The frequency distribution of women treated with 2000 1500 1000 500 Statistical analysis 0 Ser/Ser 150 U/day FSH Ser/Ser Asn/Asn 225 U/day FSH 150 U/day FSH 10 000 Oestradiol (pmol/l) Statistical calculations were performed by SigmaStat for Windows. version 2.001) (Fig. Differences between groups were tested by one-way analysis of variance (ANOVA). group II: 6. differences between the individual groups were analysed by a posteriori Student–Newman–Keuls (SNK) tests.028). n = 44) of the FSH receptor (lower panel: *significant difference between group I and III). independently of the total FSH dose applied. This confirms that women in group II were indeed exposed to a 50% higher amount of FSH compared to groups I and III. Increasing the FSH stimulation dose from 150 to 225 U/day was able to overcome the lower oestradiol response in women with the Ser/Ser FSH receptor variant (group II. Differences in frequency distribution of recombinant versus urinary FSH and GnRH agonists versus antagonists. The sensitivities of the assays were 0. . n = 44: 32. 1.4 U/l. n = 25: 33.and interassay coefficient of variations were < 3% and < 7% for FSH and oestradiol.9 ± 0. recombinant versus urinary FSH and of women treated with GnRH agonist versus antagonist was similar in the three groups (P = NS. respectively. In particular. 1 3000 Results Age (group I. ANOVA: P = 0. As shown in Table 1. group II.6 years. lower panel). using the Autodelfia system (Perkin Elmer. lower panel). This difference in ovarian response could be overcome by increasing the daily FSH dose from 150 U/day to 225 U/day (upper panel: *significant higher total FSH dose) in women with the Ser/Ser allele variant (group II. Germany). Illinois. Total FSH doses for ovarian stimulation were comparable in group I (1631 ± 96 U) and group III (1640 ± 57 U). For the variables oestradiol serum concentration and duration of FSH stimulation.5 U/l. 1. P > 0. group III.03 (SPSS Inc. All variables were checked for normal distribution by the Kolmogorov–Smirnov test and equal variance.9 ± 0. Chicago. n = 24) compared to the Asn/Asn allele variant (group III.05. Serum levels of oestradiol before ovulation induction were significantly lower in women with the Ser/Ser allele variant (group I. and differences in pregnancy rates between study groups. Copyright © Lippincott Williams & Wilkins.7 ± 0. in the presence of no difference in the total duration of FSH stimulation (Table 1). lower panel: no significant difference between group II and III. 453 Serum FSH and oestradiol were measured by immunofluorimetric assay and by fluorimmunoassay. 7804 ± 983 pmol/l) (SNK test: group II versus III. Freiburg. Fig. n = 24: 32.72) were not different between groups. were tested by the chi-square test. USA). 1.7 ± 0. analysis was performed on log-transformed data to achieve normal distribution.7 ± 0. chi-squared) (Table 2). oestradiol levels were significantly lower in group I (5680 ± 675 pmol/l) compared to group III (8679 ± 804 pmol/l) (SNK test: group I versus III. The results are shown as means ± SEM. Oestradiol levels on the day of hCG administration were significantly different among the three groups (ANOVA: P = 0. upper panel).7 years.3 U/l. no differences were seen between the groups for number of follicles. n = 25).05 (two-tailed) was considered statistically significant. retrieved oocytes.05) (Fig. the respective analysis was performed by Kruskal–Wallis oneway ANOVA with Dunn’s method. upper panel) and oestradiol levels (lower panel) in the three study groups.7 years. respectively. Because no normal distribution by logtransformation could be achieved for the variables total FSH stimulation dose and cumulative embryo score. ∗ 2500 Total FSH dose (U) Hormone analysis 8000 ∗ 6000 4000 2000 0 Ser/Ser 150 U/day FSH Group I Ser/Ser 225 U/day FSH Group II Asn/Asn 150 U/day FSH Group III Total follicle-stimulating hormone (FSH) dose (mean ± SEM. as described previously [11].05 IU/l and 25 pmol/l for FSH and oestradiol.

225 U/day FSH Group III: Asn/Asn.e follicular development and stimulation of oestradiol production) might be uncoupled and/or involve different downstream pathways of the FSH receptor. 150 U/day FSH 32. No woman experienced severe OHSS.7 5.51 0. a hypothesis which might be investigated in granulosa cells retrieved from women undergoing COH. Despite differences in oestradiol levels. In the present study. It is tempting to speculate that the p. In addition. Discussion This prospective interventional study is the first randomized controlled trial to demonstrate a differential oestradiol response to FSH due to the SNP at nucleotide position 2039 of the FSH receptor gene.7 6.7 (1–22) 53. we demonstrated that women homozygous for Ser at codon 680 have significantly higher serum FSH levels between the luteal-follicular transition up to ovulation than women homozygous for Asn.4) (6–21) (1–25) 33. These results confirm previous data obtained by us and by other groups in retrospective.6 10. These data demonstrate convincingly that FSH is less efficient in women with the p.9) (7–18) (3–29) 10.2–9. development of multiple follicles and rapid increase of oestradiol levels) are wellknown risk factors [14].80 Data are mean ± SEM (range) and proportions. which were not the primary end point and require much larger multicentre trials.4 ± 4. this is not surprising because women with FSH levels >10 IU/l were excluded and the number of subjects considered was much lower in the present study.79 0. in the presence of similar serum oestradiol levels (Greb et al.1–38. in a very recent study involving menstrual cycle monitoring in women with normal.6 5.6 ± 7.82 0. In any case.52 0.9 (0–100) 26.1 8.1 (4–64) 4/25 Group III: Asn/Asn. a potentially life-threatening condition.39 0.9 ± 0.8 (2–96) 10/44 P 0.454 Pharmacogenetics and Genomics 2005. A recent retrospective association study demonstrated that the FSH receptor p. FSH stimulates expression of LH receptors [12]. Oestradiol production depends on the availability of androgen substrate. indicating that the two main functions of FSH (i. 150 U/day FSH P 22/2 19/5 23/2 19/6 37/7 39/5 0.N680S FSH receptor sequence variation.e.7) (2.9 ± 0. This finding is of major clinical relevance because women homozygous for Asn at codon 680 who are stimulated with the same amount of FSH as women homozygous for Ser will achieve significantly higher oestradiol levels. We are able to show that the same FSH dose for COH results in significantly lower serum levels of oestradiol in women homozygous for Ser/Ser at codon position 680 compared to women homozygous for Asn/Asn.5 ± 3.2 ± 0. .7 ± 0. hCG.35 fertilization rate.8 (25.. In addition. cumulative embryo score.3 ± 1. the present study was not powered to address possible differences in these parameters.7 ± 0. Human chorionic gonadotrophin. which is luteinizing hormone (LH)-dependent.30 0. 150 U/day FSH Group II: Ser/Ser.7 ± 0. fertilization rate.9 (0–17) 58.4 10. 150 U/day FSH Age of the women (years) Early follicular phase FSH (U/l) Duration of FSH stimulation (days) Ovarian follicles > 10 mm diameter before hCG administration (n) Retrieved oocytes (n) Fertilization rate (%) Cumulative embryo score Clinical pregnancy rate 32.1 ± 0. at least in terms of oestradiol production.4) (7–16) (4–23) 11. cross-sectional trials [6– 9]. Unauthorized reproduction of this article is prohibited.0 ± 1. At odds with our previous study [6].2 ± 2.3 11. the response to gonadotropin stimulation (i. Table 2 Number of patients treated with recombinant versus urinary follicle-stimulating hormone (FSH) as well as gonadotrophinreleasing hormone (GnRH) agonist versus antagonist in each study group Recombinant/urinary FSH GnRH agonist/antagonist Group I: Ser/Ser. unpublished data).72 0.2 ± 1.2 (8–100) 28.25 0.1 Group II: Ser/Ser.7 ± 0.3) (2. 225 U/day FSH (25. no significant differences were detected in the number of follicles or retrieved oocytes. the decreased sensitivity of the FSH receptor regarding oestradiol production could be overcome by a 50% increase of the exogenous FSH dose.9 (4–48) 5/24 (26.3 ± 0.6–9. However.N680S variant was significantly more represented in women developing iatrogenic OHSS but that the wild-type allele was significantly associated with the severity of OHSS Copyright © Lippincott Williams & Wilkins.7 (0–100) 29.4 12. respectively. cumulative embryo score and pregnancy rate were similar in the three groups. which might affect adequate endometrial maturation in these patients [13] or might even put them at greater risk for OHSS.1 ± 0.5 ± 2.5–39.3–39.N680S FSH receptor is less effective in inducing LH receptor and/or aromatase expression.5 10. Vol 15 No 7 Table 1 Baseline characteristics and results of controlled ovarian hyperstimulation depending on follicle-stimulating hormone (FSH) stimulation dose and FSH receptor genotype in the three study groups Group I: Ser/Ser. However. non-randomized.2 ± 5. Although FSH itself is not responsible for OHSS.9 ± 0. our data suggest that differences in oestradiol levels due to the FSH receptor polymorphism do not appear to have major effects on IVF/ICSI outcome.1 (2–25) 62.5 11. day 3 serum FSH levels were not different among the groups. and clinical pregnancy rate. mono-ovulatory cycles.8 ± 0.6) (2.0–9.

Kudo M. Tapanainen J. 455 [15]. 5 Aittomaki K. Sato O. Age and day 3 FSH levels have been used as an indicator of ovarian response in ART. 8:893–899. Kamischke A. Nieschlag E. et al. 9 de Castro F. et al. corroborating our original finding [6]. Differentiating clinical profiles: predicting good responders. 6:361–366. Mol Hum Reprod 2002. Reprod Biol Endocrinol 2004. 84:751–755. Hsueh AJ. Notwithstanding its drawbacks. Among them. this FSH receptor SNP should be considered before starting COH for IVF/ICSI. Rosenwaks Z. Copyright © Lippincott Williams & Wilkins. Sistonen P. Pharmacogenetics 2004. Knowing these limits. 18:739–773. In conclusion. Reprod Biomed Online 2003. Such a trial could effectively analyse the ovarian response in terms not only of oestradiol concentrations. based on the same FSH and analog preparation. Genetic and functional analyses of polymorphisms in the human FSH receptor gene. antral follicle count and ovarian volume are useful in predicting ovarian response to hormone stimulation [16]. 8 de Castro F. Gromoll J. The available data of the literature support our conclusion. Ovarian response to follicle-stimulating hormone (FSH) stimulation depends on the FSH receptor genotype. pregnancy rate. Ruiz R. poor responders. 14:285–293. In perspective. . Nieschlag E. this randomized. 2 Kligman I. in press. Gromoll J. and pathophysiology. Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Gromoll J. et al. 6 Perez Mayorga M. J Clin Endocrinol Metab 1999. 85:3365–3369. Unauthorized reproduction of this article is prohibited. the number of poor responders to FSH stimulation in IVF/ICSI cycles was significantly higher in women with the Ser/Ser variant compared to the Asn/Asn and Asn/Ser variants [8]. but also of follicular growth. Nieschlag E. Individual patients with Asn/Asn at codon 680 achieving high levels of oestradiol and potentially other ovarian factors could be at increased risk for the severe OHSS. should be applied. Lucena JL. More recently. Sta¨hle D. The individual response to FSH stimulation in COH is rather variable and many studies have attempted to identify predictive factors of ovarian response that could be useful in determining the gonadotropin stimulation protocol and the FSH starting dose. our study has a number of limitations that need to be considered. 76:1185–1190. and hyperresponders. J Clin Endocrinol Metab 2000. physiology. Nieschlag E. Wada S. Gromoll J. Sanchez-Casas Padilla E. The physiology of follicle selection. Padilla ES. Wunsch A. Asatiani K. Admittedly. the present study has proven that a common FSH receptor SNP influences ovarian response to FSH in COH. in women with normal ovarian function undergoing ART. these patients. including severe OHSS. the relatively low number of subjects. Nieschlag are gratefully acknowledged. 82: 959–968. the exclusion of heterozygous women. Simoni M. Real LM. Hum Reprod Update 2002. with higher sensitivity for oestradiol production. Zitzmann M. Therefore. in which heterozygous women should be considered as well and a fixed protocol. multicentre trials to determine whether such a pharmacogenetic approach to ovarian stimulation will prove advantageous both in terms of number of live births and safety. A short review of ovarian stimulation in assisted reproductive techniques. number of live births and side-effects. References 1 Cohen J. at least in women with normal ovarian function. controlled study demonstrates a differential response of serum oestradiol levels in women receiving FSH for COH. In addition. Role of follicle-stimulating hormone receptor Ser680Asn polymorphism in the efficacy of follicle-stimulating hormone. other factors. Isoforms and single nucleotide polymorphisms of the FSH receptor gene: implications for human reproduction. Moron FJ. 10 Ahda Y. Perez-Hernandez D. we chose a primary end point (serum oestradiol level) for which the study was sufficiently powered.Pharmcogenetics of FSH treatment Behre et al. Larger numbers of patients can be achieved only with much larger multicentre trials. comparable daily and total exogenous FSH doses result in similar follicular growth but in different oestradiol serum levels depending on the FSH receptor allele variant at codon 680. Together with our data. Simoni M. Montoro L. Fujimoto S. This should be investigated further in large prospective. Galan JJ. 8:413–421. Human controlled ovarian hyperstimulation outcome is a polygenic trait. molecular biology. have been considered [17]. One recent non-randomized study found significantly lower oestradiol levels per retrieved oocyte in women with the Ser/Ser variant treated by high hMG doses in IVF cycles [7]. Gromoll J. 2:31. randomized. Mutational analysis of the follicle-stimulating hormone (FSH) receptor in normal and infertile men: identification and characterization of two discrete FSH receptor isoforms. number of oocytes retrieved. Hernandez DP. FSH receptor gene haplotype distribution in normozoospermic and azoospermic men. 3 Simoni M. 11 Simoni M. Gassner C. these findings strongly suggest that women with Asn at codon 680 undergoing COH for IVF/ICSI are at risk of excessive stimulation with FSH. might have a decreased follicular response and lower numbers of retrievable oocytes because of lower exogenous FSH administration. Acknowledgements The skilful technical assistance of N. In another non-randomized study. Our data suggest that the FSH receptor exon 10 SNP should be considered as well. Behre HM. Montoro L. Conversely. 7 Sudo S. Endocr Rev 1997. such as serum inhibin B and antimullerian hormone concentrations. Krafft T. and the use of different FSH and GnRH analog preparations should be mentioned. et al. which might result in severe iatrogenic OHSS. 4 Simoni M. J Androl 2005. Fertil Steril 2003. These results are of immediate clinical relevance for infertile women treated by ART. if treatment cycles are primarily monitored by serum levels of oestradiol. Terwort and the language editing of S. The follicle-stimulating hormone receptor: biochemistry. Fertil Steril 2001. 80:571–576. Gromoll J. Cell 1995. it might be possible to define the optimal FSH starting dose based on the simple determination of the FSH receptor genotype. Ho¨ppner W. 12 Zeleznik AJ. If treatment cycles are primarily monitored by ultrasonography of ovarian follicular development. Pakarinen P.

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