http://humrep.oxfordjournals.org/content/18/12/2698.full
Luteal estradiol pre‐treatment coordinates follicular growth during controlled ovarian hyperstimulation with GnRH antagonists
- Renato Fanchin1,3,
- Laurent Salomon1,
- Altina Castelo‐Branco1,
- François Olivennes1,
- Nelly Frydman2 and
- René Frydman1
+Author Affiliations
- 3To whom correspondence should be addressed at: Department of Obstetrics and Gynecology and Reproductive Medicine, Hôpital Antoine Béclère, 157, rue de la Porte de Trivaux, 92141 Clamart, France. e‐mail: renato.fanchin@abc.ap‐hop‐paris.fr
- Received July 30, 2003.
- Accepted October 8, 2003.
Abstract
BACKGROUND: The purpose of this study was to investigate whether luteal estradiol (E2) administration reduces follicular size discrepancies and enhances ovarian response in recombinant FSH (r‐FSH)/GnRH antagonist protocols. METHODS: We studied prospectively 90 IVF‐embryo transfer (ET) candidates who were randomly pre‐treated with 17β‐E2 (4 mg/day) from day 20 until next cycle day 2 (E2 group, n = 47) or served as controls (control group, n = 43). On day 3, all women started r‐FSH treatment. A single 3 mg dose of GnRH antagonist was administered eventually according to follicular maturation. Outcome measures were magnitude of size discrepancy of growing follicles on day 8 of r‐FSH treatment and number of follicles ≥16 mm in diameter on the day of HCG. RESULTS: On day 8, follicles were smaller (9.9 ± 2.5 versus 10.9 ± 3.4 mm,P < 0.001) and their size discrepancies attenuated (P < 0.001) in the E2 group compared with the control group. This was associated with more ≥16 mm follicles, mature oocytes and embryos in the E2 group. CONCLUSIONS: Luteal E2administration reduces the pace of growth, improves size homogeneity of antral follicles on day 8 of r‐FSH treatment and increases the number of follicles reaching maturation at once. Coordination of follicular development optimizes ovarian response to r‐FSH/GnRH antagonist protocols and may constitute an attractive approach to improving their outcome.
Figure 1. Study protocol. Horizontal black bars represent menstrual bleeding. Note that in the luteal E2 group, r‐FSH treatment was started on the day after 17β‐E2 discontinuation.
Table I.
Follicular development and embryological results in women pre‐treated or not with E2 during the luteal phase
Luteal E2 group | Control group | P | |
No. of follicles >10 mm on day 8 | 16.4 ± 1.0 | 16.8 ± 0.9 | NS |
Mean follicular size on day 8 (mm) | 9.9 ± 0.2 | 11.1 ± 0.3 | <0.001 |
CV of follicular sizes on day 8 | 0.22 | 0.26 | <0.02 |
Day of GnRH antagonist administration | 9.1 ± 0.2 | 8.5 ± 0.2 | <0.01 |
Day of HCG administration | 11.9 ± 0.2 | 10.8 ± 0.2 | <0.001 |
No. of follicles ≥16 mm on day of HCG | 9.9 ± 0.5 | 7.9 ± 0.5 | <0.01 |
No. of mature follicles | 9.3 ± 0.7 | 7.3 ± 0.5 | <0.03 |
No. of available embryos | 6.4 ± 0.6 | 4.6 ± 0.3 | <0.01 |
No. of embryos transferred | 2.6 ± 0.1 | 2.7 ± 0.1 | NS |
Clinical pregnancy rates/cycle | 34% | 25% | NS |
CV = coefficient of variation.
Figure 2. Hormonal dynamics during COH in luteal E2 and control groups. Baseline corresponds to the third day of the cycle (the day after E2 discontinuation in the luteal E2 group), before r‐FSH treatment. Days 6 and 8 correspond to the sixth and eighth days of r‐FSH treatment, respectively. Differences in serum E2 levels between both groups were statistically significantly at baseline (P < 0.001), on day 6 (P < 0.02) and on day 8 (P < 0.03), but not on the day of HCG. Differences in serum progesterone and LH levels between both groups did not reach statistical signification on any observation day.
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