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Manipulation of Human Ovarian Function: Physiological Concepts and Clinical Consequences¹

Division of Reproductive Medicine, Department of Obstetrics and Gynecology, Dijkzigt Academic Hospital and Erasmus University Medical School, Rotterdam, The Netherlands

I. Introduction

II. Dynamics of Normal Human Follicle Growth and Selection

A. Gonadotropin-independent and -dependent follicle growth

B. Intrafollicular endocrine changes

C. Are estrogens needed for follicle development?

D. In vivo regulation of follicle maturation in the monkey

E. The FSH threshold and window concept for in vivo follicle growth

1. FSH threshold and follicle recruitment

2. FSH window and single dominant follicle selection

3. Dominant follicle development

F. Modulation of FSH action

1. Heterogeneity of FSH

2. Direct interference with FSH action

3. Intraovarian interference with FSH action by growth factors

III. Gonadotropin Induction of Ovulation

A. The concept of monofollicle growth in anovulatory patients

B. Conditions affecting treatment outcome

1. Patient-related factors

2. Hormone preparation-related factors

3. Other factors involved

C. Commonly used step-up dose regimens

1. Conventional step-up protocol

2. Low-dose, step-up protocol

D. Potential for a step-down dose regimen

IV. Steroid Contraception and Residual Ovarian Activity

A. The concept of follicle growth during partial and transient suppression of circulating FSH

B. Ovarian suppression during steroid contraception

1. Significance of initiation of pill intake and duration of treatment

2. Comparison of different steroid doses, compounds, and regimens

3. Pill-free interval and pill omission

C. Follicle growth dynamics during steroid contraceptive regimens

D. Alternative strategies for contraceptive development

V. Conclusions and Future Directions