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Simplifying superovulation and intrauterine insemination treatment: evidence and clinical decision making
FERTILITY AND STERILITY威 VOL. 82, NO. 1, JULY 2004 Copyright ©2004 American Society for Reproductive Medicine Published by Elsevier Inc. Printed on acid-free paper in U.S.A.
Simplifying superovulation and intrauterine insemination treatment: evidence and clinical decision making Paul Claman, M.D. Division of Reproductive Medicine, Department of Obstetrics and Gynecology, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada
It is not always possible to develop a well-powered, randomized controlled trial (RCT) that will control for all possible variables to compare various treatment protocols. In the absence of evidence, it is reasonable to rely on physiologic principles, empiric observation, and, when possible, the results of an RCT to evaluate critical parts of a treatment protocol. On the basis of these principles, it is clear that a single IUI after mild superovulation done anywhere between 32 and 40 hours after hCG administration is an effective if not an efficacious treatment for idiopathic or mild male factor infertility. (Fertil Steril威 2004;82:32–3. ©2004 by American Society for Reproductive Medicine.)
After more than 2 years of idiopathic or male factor infertility, the monthly chance of pregnancy is 1%–2% without treatment (1). In these circumstances it has been shown with various stimulation and IUI protocols that superovulation together with IUI (SO-IUI) yields pregnancy rates of 10%–15% per treatment cycle (2), which is dramatically higher than with expectant management.
Received March 8, 2004; revised and accepted March 8, 2004. Reprint requests: Paul Claman, M.D., Department of Obstetrics and Gynecology, The Ottawa Hospital, Civic Campus, 737 Parkdale Avenue, Suite 505, Ottawa, Ontario K1Y4E9, Canada (FAX: 613-761-4678; E-mail: [email protected]). 0015-0282/04/$30.00 doi:10.1016/j.fertnstert.2004. 03.017
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In this issue of Fertility and Sterility, Ian Cooke (3) points out that the number of variables potentially affecting both the safety and efficacy of SO-IUI is so large that it is really impossible to use a meta-analysis to understand the outcomes of SO-IUI treatment (3). Ragni et al. (4) elegantly outline how the requirements for an adequately powered randomized controlled trial (RCT) that would control for all potential variables to study various SO-IUI intervals are almost impossible to meet. With this in mind, it is indeed unlikely that a largeenough RCT to find the best possible protocols for SO-IUI therapy will ever be completed. The cornerstone for evidence-based medicine is the RCT. The evidence-based approach, begun only 30 years ago, has been one of the most important developments in medicine (5). There are, however, still occasions when absolute proof of efficacy is impossible to obtain. In these circumstances it is incumbent on the physician to make recommendations regarding
treatment on the basis of physiologic principles and empiric, thoughtful observation. On the basis of these principles and the published studies of earlier investigators, we designed an RCT to study the interval between hCG administration and a single IUI after superovulation in the management of idiopathic and mild male factor infertility of ⱖ2 years’ duration. We chose to compare an interval of 32– 40 hours because these times are in current use by various clinics, yet there has been a suggestion in the literature that the longer hCG– IUI interval might yield superior pregnancy rates. After almost 6 years in our busy referral center clinic, we had randomized 348 patients and at the end had 270 analyzable treatment cycles (6). We found a pregnancy rate of 15%– 20% per treatment cycle without any differences between the 32- and 40-hour hCG–IUI interval groups. It is not possible to prove that a single IUI done between 32 and 40 hours after hCG administration after mild superovulation is as efficacious as more complex protocols. However, a single IUI with flexible timing for IUI is an effective way of managing these infertility problems while minimizing costs by reducing the number of IUI procedures and providing a flexible schedule to better manage clinic staffing in addition to improving convenience for the patient (7).
References 1. Wichman L, Lsoal J, Tuohimaa P. Prognostic variables in predicting pregnancy. A prospective follow up study of 907 couples with an infertility problem. Hum Reprod 1994;9:1102–8. 2. Osuna C, Matorras R, Pijoan JI, Rodriguez-Escudero FJ. One versus two inseminations per cycle in intrauterine insemination with sperm from patients’ husbands: a systematic review of the literature. Fertil Steril 2004;82:17–24. 3. Cooke ID. Randomized studies in intrauterine insemination. Fertil Steril 2004;82:27–9.
FERTILITY & STERILITY威
4. Ragni G, Somigliana E, Vegetti W. Timing of intrauterine insemination: where are we? Fertil Steril 2004;82:25–6. 5. Thomas L. The youngest science: notes of a medicine-watcher. New York: Viking Press, 1983. 6. Claman P, Wilkie V, Collins D. Timing intrauterine insemination either 33 or 39 hours after administration of human chorionic gonadotropin yields the same pregnancy rates after superovulation therapy. Fertil Steril 2004;82:13–6. 7. Guzick DS. For now, one well-timed intrauterine insemination is the way to go. Fertil Steril 2004;82:30 –1.
33
Simplifying superovulation and intrauterine insemination treatment: evidence and clinical decision making Paul Claman, M.D. Division of Reproductive Medicine, Department of Obstetrics and Gynecology, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada
It is not always possible to develop a well-powered, randomized controlled trial (RCT) that will control for all possible variables to compare various treatment protocols. In the absence of evidence, it is reasonable to rely on physiologic principles, empiric observation, and, when possible, the results of an RCT to evaluate critical parts of a treatment protocol. On the basis of these principles, it is clear that a single IUI after mild superovulation done anywhere between 32 and 40 hours after hCG administration is an effective if not an efficacious treatment for idiopathic or mild male factor infertility. (Fertil Steril威 2004;82:32–3. ©2004 by American Society for Reproductive Medicine.)
After more than 2 years of idiopathic or male factor infertility, the monthly chance of pregnancy is 1%–2% without treatment (1). In these circumstances it has been shown with various stimulation and IUI protocols that superovulation together with IUI (SO-IUI) yields pregnancy rates of 10%–15% per treatment cycle (2), which is dramatically higher than with expectant management.
Received March 8, 2004; revised and accepted March 8, 2004. Reprint requests: Paul Claman, M.D., Department of Obstetrics and Gynecology, The Ottawa Hospital, Civic Campus, 737 Parkdale Avenue, Suite 505, Ottawa, Ontario K1Y4E9, Canada (FAX: 613-761-4678; E-mail: [email protected]). 0015-0282/04/$30.00 doi:10.1016/j.fertnstert.2004. 03.017
32
In this issue of Fertility and Sterility, Ian Cooke (3) points out that the number of variables potentially affecting both the safety and efficacy of SO-IUI is so large that it is really impossible to use a meta-analysis to understand the outcomes of SO-IUI treatment (3). Ragni et al. (4) elegantly outline how the requirements for an adequately powered randomized controlled trial (RCT) that would control for all potential variables to study various SO-IUI intervals are almost impossible to meet. With this in mind, it is indeed unlikely that a largeenough RCT to find the best possible protocols for SO-IUI therapy will ever be completed. The cornerstone for evidence-based medicine is the RCT. The evidence-based approach, begun only 30 years ago, has been one of the most important developments in medicine (5). There are, however, still occasions when absolute proof of efficacy is impossible to obtain. In these circumstances it is incumbent on the physician to make recommendations regarding
treatment on the basis of physiologic principles and empiric, thoughtful observation. On the basis of these principles and the published studies of earlier investigators, we designed an RCT to study the interval between hCG administration and a single IUI after superovulation in the management of idiopathic and mild male factor infertility of ⱖ2 years’ duration. We chose to compare an interval of 32– 40 hours because these times are in current use by various clinics, yet there has been a suggestion in the literature that the longer hCG– IUI interval might yield superior pregnancy rates. After almost 6 years in our busy referral center clinic, we had randomized 348 patients and at the end had 270 analyzable treatment cycles (6). We found a pregnancy rate of 15%– 20% per treatment cycle without any differences between the 32- and 40-hour hCG–IUI interval groups. It is not possible to prove that a single IUI done between 32 and 40 hours after hCG administration after mild superovulation is as efficacious as more complex protocols. However, a single IUI with flexible timing for IUI is an effective way of managing these infertility problems while minimizing costs by reducing the number of IUI procedures and providing a flexible schedule to better manage clinic staffing in addition to improving convenience for the patient (7).
References 1. Wichman L, Lsoal J, Tuohimaa P. Prognostic variables in predicting pregnancy. A prospective follow up study of 907 couples with an infertility problem. Hum Reprod 1994;9:1102–8. 2. Osuna C, Matorras R, Pijoan JI, Rodriguez-Escudero FJ. One versus two inseminations per cycle in intrauterine insemination with sperm from patients’ husbands: a systematic review of the literature. Fertil Steril 2004;82:17–24. 3. Cooke ID. Randomized studies in intrauterine insemination. Fertil Steril 2004;82:27–9.
FERTILITY & STERILITY威
4. Ragni G, Somigliana E, Vegetti W. Timing of intrauterine insemination: where are we? Fertil Steril 2004;82:25–6. 5. Thomas L. The youngest science: notes of a medicine-watcher. New York: Viking Press, 1983. 6. Claman P, Wilkie V, Collins D. Timing intrauterine insemination either 33 or 39 hours after administration of human chorionic gonadotropin yields the same pregnancy rates after superovulation therapy. Fertil Steril 2004;82:13–6. 7. Guzick DS. For now, one well-timed intrauterine insemination is the way to go. Fertil Steril 2004;82:30 –1.
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