Are laparoscopic ovarian diathermy and gonadotropin administration the only therapeutic second-steps in clomiphene-citrate resistant women with polycystic ovary syndrome?
1 Department of Obstetrics & Gynecology, University ‘Magna Graecia’, Catanzaro and 2 Department of Molecular & Clinical Endocrinology and Oncology, University ‘Federico II’, Naples, Italy
3 To whom the correspondence should be addressed. Email: stefanopalomba{at}tin.it
Dear Sir,
We have read with very deep interest the paper by van Wely et al. (2004)
recently published in Human Reproduction, reporting an economic comparison between two approaches to inducing ovulation in clomiphene-citrate (CC) resistant polycystic ovary syndrome (PCOS) women. In particular, a classical laparoscopic electrocautery strategy, consisting of laparoscopic ovarian diathermy (LOD) followed by CC and then gonadotropins, has been compared with recombinant FSH (rFSH) administration. The authors concluded that the two therapeutic strategies have the same effectiveness, but the laparoscopic electrocautery strategy is less expensive.
We would like to comment on some aspects of the study.
In the abstract and in the introduction it is stated that rFSH is the current standard treatment for ovulation induction in PCOS women who do not respond to clomiphene-citrate treatment. I feel that this statement is not evidence medicine based (Nugent et al., 2000; van Wely et al., 2003). In fact, in two recent systematic reviews (Nugent et al., 2000; van Wely et al., 2003) it was concluded that, in PCOS women, there is no evidence of a significant difference between human menopausal gonadotropins (HMG) and urinary FSH (uFSH), and between uFSH and rFSH in any of the outcomes evaluated.
Based on these considerations and in an economic prospective, we think that a comparison between LOD (followed by CC and then gonadotropins) and HMG or uFSH should be more appropriate.
According to Bayram et al. (2004), diagnostic laparoscopy could be omitted in the management of infertile women with PCOS without suspected peritoneal disease. Furthermore, we suggest that, at the moment, LOD should be performed only in oligo-anovulatory PCOS women with associated gynecological disease (uterine leiomyomas, endometriosis, pelvic adhesions, etc.).
Pirwany and Tulandi (2003) have shown that a new treatment, i.e. metformin cloridrate administration, is effective in inducing ovulation in CC-resistant or not-resistant PCOS women. Furthermore, given the high success rate and the safety of CC, metformin use is not appropriate as a first-step treatment for ovulation induction in PCOS women. Contrary to gonadotropins administration, both LOD and metformin administration are characterized by few side-effects, by the simplicity of management due to no need for ongoing monitoring, and by a positive impact at endocrine and metabolic level. In support of this view, we have recently demonstrated that in CC-resistant women with PCOS, 1 year metformin treatment is as effective as LOD in terms of ovulation induction (Palomba et al., 2004). A significant advantage of metformin administration was detected in terms of pregnancy, abortion and live-birth rates (Palomba et al., 2004). Finally, 1 year of metformin treatment was shown to be 
10-fold less expensive than LOD (Palomba et al., 2004).
Unfortunately, in the paper by van Wely et al. (2004) no comment on this new therapeutic option was made.
References
Bayram N, van Wely M, Kaaijk EM, Bossuyt PM and van der Veen F (2004) Using an electrocautery strategy or recombinant follicle stimulating hormone to induce ovulation in polycystic ovary syndrome: randomised controlled trial. BMJ 328, 192–197.
Nugent D, Vandekerckhove P, Hughes E, Arnot M and Lilford R (2000) Gonadotrophin therapy for ovulation induction in subfertility associated with polycystic ovary syndrome. Cochrane Database Syst Rev 4 CD000410.
Palomba S, Orio F Jr, Nardo LG, Falbo A, Russo T, Corea D, Doldo P, Lombardi G, Colao A and Zullo F (2004) Metformin administration versus laparoscopic ovarian diathermy in clomiphene citrate-resistant women with polycystic ovary syndrome: a prospective parallel randomized double-blind placebo-controlled trial. J Clin Endocrinol Metab (in press).
Pirwany I and Tulandi T (2003) Laparoscopic treatment of polycystic ovaries: is it time to relinquish the procedure? Fertil Steril 80, 241–251.[Web of Science][Medline]
van Wely M, Bayram N and van der Veen F (2003) Recombinant FSH in alternative doses or versus urinary gonadotrophins for ovulation induction in subfertility associated with polycystic ovary syndrome: a systematic review based on a Cochrane review. Hum Reprod 18, 1143–1149.
van Wely M, Bayram N, Van Der Veen F and Bossuyt PM (2004) An economic comparison of a laparoscopic electrocautery strategy and ovulation induction with recombinant FSH in women with clomiphene citrate-resistant polycystic ovary syndrome. Hum Reprod 9, 1741-1745.
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