Human Reproduction Update, Vol.9, No.3 pp.263-274, 2003
© European Society of Human Reproduction and Embryology 2003; all rights reserved
Mono-ovulatory cycles: a key goal in profertility programmes
1 A meeting was organized by ESHRE (Capri, September 1–2, 2002) with financial support from Ferring Pharmaceuticals to discuss the above subjects. The speakers included D.T.Baird (Edinburgh), J.Collins (Hamilton), P.G.Crosignani (Milano), J.L.H.Evers (Maastricht), R.Fanchin (Clamart), B.C.Fauser (Rotterdam), M.Filicori (Bologna), H.Jacobs (London), B.Tarlatzis (Thessaloniki). The discussants included: J.Cohen (Paris), E.Diczfalusy (Rönninge), K.Diedrich (Lubeck), L.Fraser (London), G.C.Frigerio (Milano), L.Gianaroli (Bologna), J.Harlin (Stockholm), J.Persson (Copenhagen), A.Rojas-Rìos (Copenhagen), A.Sunde (Trondheim), A.Van Steirteghem (Bruxelles). The report was prepared by J.Collins (Hamilton) and P.G.Crosignani2 (Milano).
To whom correspondence should be addressed at: 2P.G.Crosignani, e-mail: piergiorgio.crosignani{at}unimi.it
Abstract
Mono-ovulatory cycles for women are optimal because singleton pregnancies have a better outcome than multiples. Multiple births began to increase in the 1950s after the first appearance of effective ovulation induction for the treatment of anovulation. Since the 1980s when ovulation induction and IVF were more broadly applied to the treatment of unexplained and persistent infertility, there has been an unprecedented rise in multiple births. Strategies to achieve mono-ovulation during treatment of anovulatory patients are distinct from those for the treatment of ovulating patients who have unexplained and persistent infertility. Anovulatory patients with hypogonadotrophic hypogonadism can be treated with exogenous pulsatile GnRH, which restores normal gonadotrophin secretion, ovulation rates and conception rates. The multiple pregnancy rate is not increased with GnRH treatment. In patients with normogonadotrophic anovulation, attention should be given to diet and exercise before any other interventions are considered. Pharmacological induction of ovulation can be achieved with antiestrogen, gonadotrophin or pulsatile GnRH treatment; antiestrogen is the first choice with gonadotrophin more widely used for clomiphene citrate (CC)-resistant patients. Obesity and polycystic ovaries are common in this group, so that gonadotrophin and GnRH treatment are associated with lower responses compared with hypogonadotrophic hypogonadism, and higher multiple pregnancy rates. Low dosage protocols are being tested that may lower the multiple birth rates. The role of drugs enhancing sensitivity to insulin, e.g. metformin, remains undetermined. Laparoscopic ovarian diathermy achieves conception rates that are equivalent to gonadotrophin treatment, with fewer multiple births. Augmenting normal ovulation processes for couples with unexplained and persistent infertility is less effective. Pregnancy rates are statistically significantly higher with CC but the size of the increase is not clinically important. CC with intrauterine insemination is associated with a clinically important effect on conception. Achieving mono-ovulation is more difficult in assisted reproductive technology cycles because success depends on maintaining the level of FSH above the threshold level longer than normal in order to increase the number of mature follicles. Milder stimulation for IVF and IVF in the untreated cycle show great potential, however, especially in view of the trend toward transfer of a single embryo in assisted reproductive treatment cycles.
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