Brooks, Alan Arnold; (1996) Investigation of endometrial response to hormone therapy in oocyte recipients. Doctoral thesis (M.D), UCL (University College London).

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Abstract

Ovum donation has been performed successfully over the last decade using several different hormone replacement regimens. The overall live birth rate is of the order of 30% per treatment cycle, which compares favourably with that following natural conception and better than that seen following in-vitro fertilisation with the mother's own oocytes. Those who fail to become pregnant following ovum donation may have a sub-optimal response to hormone replacement therapy (HRT). However, the efficacy of different HRT regimens has not been investigated previously in a systematic and comprehensive manner. Indeed, most regimens have evolved empirically. The standard HRT regimen used at the Lister Fertility Clinic, London, is one such empirical regimen, but despite this, has proved successful.In order to provide a scientific basis for the design of HRT regimens for oocyte donation programmes, this project has investigated the effect of changing the dose or duration of oestradiol treatment on parameters that have been suggested to be related to pregnancy rate. In addition, the relationship between these parameters has also been studied. The parameters investigated are endometrial thickness, change in endometrial thickness, serum oestradiol levels, endometrial progesterone receptors, endometrial histological dating and endometrial ultrastructural characteristics. Sixty seven volunteers were randomised to one of three HRT regimens: 22 in regimen one (the standard HRT regimen); 23 in regimen two (using an increased duration of oestradiol); and 22 in regimen three (using an increased dose of oestradiol). The results did not show a significant difference between the three HRT regimens in any of the parameters investigated. Indeed, the endometrial thickness following treatment with all three HRT regimens was greater than 7.5 mm, a clinically significant threshold associated with improved pregnancy rate. A factor restricting endometrial growth was recognised but not identified. Normal progesterone receptor expression was seen in all three HRT regimens. A previously unreported persistence, and possible increase, in stromal cell progesterone receptor expression was recognised between the early and mid luteal phases. A variation in histological dating was seen in both the early and mid luteal phases of the cycle, and these dates were not correlated with each other. Ultrastructural observations suggest that a sequential maturation of endometrial cells occurs within each gland, which is not represented by classical histological dating, but may explain the prolonged 'window of implantation' seen in humans. Overall, the findings are consistent with therapy which is above the threshold level for a facilitating/activating relationship between treatment and response, and not consistent with the classical dose-response model for hormone therapy. In conclusion, in designing a HRT regimen for oocyte donation programmes, increased oestradiol dosage during the follicular phase is unlikely to result in an improved pregnancy rate above that of the standard regimen (2 mg twice daily for ten days), equally, nor is it disadvantageous to prolong oestradiol treatment (at least up to a total of 17 days) before starting progesterone treatment.

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