Revisiting the association between smoking and female fertility using the oocyte donation model.

RESEARCH QUESTION: Is active smoking among donors, recipients and male partners associated with oocyte donation cycle outcomes, in donors and recipients? DESIGN: Retrospective cohort over a 4-year period including 4747 oocyte recipients and partners, and 3101 oocyte donors. All oocyte donation cycles were carried out between 2010 and 2014, and for whom donor, recipient and male partner smoking status at the time of treatment were known. RESULTS: Ovarian response was significantly reduced in oocyte donors who smoked compared with those who did not: 13.9 (SD 6.7) mature oocytes in heavy smokers versus 14.8 (SD 7.6) in non-smokers (P = 0.020). Nevertheless, biochemical, clinical and ongoing pregnancy rates and live birth rates were not affected by the degree of smoking among donors, recipients or recipients' partners. CONCLUSIONS: This study suggests that smoking is not associated with compromised oocyte quality or altered uterine receptivity in oocyte donation cycles.

Assessment of theca cell function: a prerequisite to androgen or luteinizing hormone supplementation in poor responders.

Poor responders are a heterogeneous population, with some patients displaying a diminished ovarian reserve and others a poor ovarian reserve with preserved granulosa cell function. Androgen and LH/hCG supplementation has been advocated for poor responders, mainly those >40 years old. Although androgens synergistically act with FSH to support folliculogenesis, and ovarian androgen secretion declines with age, there is still no evidence that androgen therapy is actually effective to improve ovarian FSH sensitivity. The main reason seems to be that theca cell function has not been appropriately assessed in patients at risk of poor response. The definition of theca insufficiency is hampered by methodologic shortcomings in routine bioassays. Provocative tests for theca cells might help to identify those patients who could benefit from androgen supplementation. The lack of data regarding theca cells in these patients might contribute to explaining the absence of evidence for a positive effect of androgen therapy.

FSH and its second messenger cAMP stimulate the transcription of human anti-Müllerian hormone in cultured granulosa cells.

Anti-Müllerian hormone (AMH), also called Müllerian-inhibiting substance, a member of the TGF-ß family, is responsible for the regression of Müllerian ducts in the male fetus. In females, AMH is synthesized by granulosa cells of preantral and small antral follicles, and production wanes at later stages of follicle maturation. Using RT-PCR in luteal granulosa cells in primary culture and reporter gene techniques in the KK1 granulosa cell line, we show that FSH and cAMP enhance AMH transcription, and LH has an additive effect. Gonadotropins and cAMP act through protein kinase A and p38 MAPK signaling pathways and involve the GATA binding factor-4 and steroidogenic factor-1 transcription factors, among others. The expression profile of AMH and the dynamics of serum AMH after gonadotropin stimulation have been interpreted as a down-regulating effect of FSH upon AMH production by granulosa cells. The specific effect of gonadotropins upon granulosa cells may be obscured in vivo by the effect of FSH upon follicular maturation and by the presence of other hormones and growth factors, acting individually or in concert.