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Subfertility, fecundability, and the impact of laparoscopy on conception rates
CONTROVERSY RESPONSES Subfertility, fecundability, and the impact of laparoscopy on conception rates Alan S. Penzias, M.D. Boston IVF, Waltham; Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston; and Harvard Medical School, Boston, Massachusetts
Confusion is common when trying to compare the outcome of different fertility treatments. Calculation of fecundability is an excellent adjunct to reports that show cumulative conception totals after a period of observation or treatment. (Fertil Steril威 2005;84:1579 – 80. ©2005 by American Society for Reproductive Medicine.) Key Words: Fecundability, infertility, subfertility, in vitro fertilization
When the infertility evaluation came back “negative”— normal cycle day 3 hormone values, normal hysterosalpingogram, and normal semen analysis—the couple facing me across the desk did not seem all that reassured. She was 32 years old, ovulated regularly, and had an entirely unremarkable menstrual and medical history. He was 35 with no history of paternity and had an equally unremarkable medical history. Their disappointment to my news was understandable; after all, they had spent the better part of 2 years trying to get pregnant and they were hoping for a definitive answer. Puzzled looks followed as I explained that they were not infertile but simply suffered from subfertility. Put another way, they have a calculable chance of becoming pregnant every month but they are among a population likely to conceive at 1%–3% per month rather than 20% per cycle as seen in the general population (1). Fecundability is the chance of becoming pregnant per menstrual cycle. It’s perhaps the single most important statistic available to patients and practitioners, because it allows a head-to-head comparison of treatments. The medical literature is replete with good studies that dutifully report the cumulative percentage of patients who achieve pregnancy over a given period of time following a specified intervention. Relatively few studies, however, calculate the fecundability of the treatment population. For example, consider the following two hypothetical examples. 1) Following administration of fertility drug Omega, 67.2% of the test population conceived during the Received March 27, 2005; revised and accepted March 31, 2005. Reprint requests: Alan S. Penzias, M.D., Boston IVF, 40 Second Avenue, Suite 300, Waltham, Massachusetts 02451 (E-mail: alan.penzias@ bostonivf.com).
0015-0282/05/$30.00 doi:10.1016/j.fertnstert.2005.03.088
18 months of follow-up. 2) Following administration of fertility drug Epsilon, 77.4% of the subjects conceived within 2 years of treatment. The reader of these two studies would be hard pressed to see the treatments as equivalent, though their fecundabilies are both exactly 6%. The study in this month’s journal (2) reports a 76% conception rate (22 of 29) in a population of infertile endometriosis patients who underwent laparoscopy after having failed at least 1 cycle of IVF. The time to conception in 14 of the 22 ranged from 1 to 8 months. A similar group of patients who declined laparoscopy was used as a control population. Among those who did not have laparoscopic treatment of endometriosis, 37% conceived (13 of 35). The very reasonable cumulative conception rate in the control population should not come as a surprise. Collins et al. (3) reported on the incidence of treatment-independent pregnancy in a population of infertility patients followed for 2 to 7 years. A total of 191 of 548 untreated couples (35%) became pregnant. Furthermore, 31% of the pregnancies that occurred in treated couples were achieved 3 months after the last medical treatment or more than 12 months after adnexal surgery. In the present study the distinction between treatmentindependent and treatment-dependent pregnancy is less clear. Of the 22 patients who conceived after undergoing laparoscopic treatment for endometriosis, 12 conceived spontaneously, 2 conceived with clomid and IUI, and 8 conceived with additional IVF treatment. Time to conception data is presented for the 14 nonrepeat IVF pregnancies: 1 to 8 months. Putting aside the method used to achieve pregnancy, hypothetically if all 29 patients who underwent laparoscopy began trying to get pregnant at the same time point postop-
Fertility and Sterility姞 Vol. 84, No. 6, December 2005 Copyright ©2005 American Society for Reproductive Medicine, Published by Elsevier Inc.
1579
FIGURE 1 Cumulative percentage of population pregnant over time as a function of conception rate.
Fecundability Table
Month 1 3 6 12 18 24
Rate 20%
10%
3%
1%
20% 49%
10% 27%
3% 9%
1% 3%
74% 93% 98% 99%
47% 72% 85% 92%
17% 31% 42% 52%
6% 11% 17% 21%
Penzias. Subfertility and fecundability. Fertil Steril 2005.
eratively and 22 of them (76%) were pregnant after 8 months of attempts, the fecundability calculates to 16.5%. Stated another way, if a population of patients has a conception rate of 16.5% per month, 76% of that group will be pregnant by the end of 8 months of attempts. Using the same method to calculate the fecundability of the untreated population, and assuming that all 13 of the 35 patients in that group also conceived by the end of 8 months, the result is 5.7%. Restated, if a population of patients has a conception rate of 5.7% per month, 37% of that group will be pregnant by the end of 8 months of attempts. With comparative fecundability rates of 16.5% and 5.7%, one can then ask how long it should take the less fertile group to achieve the same 76% cumulative pregnancies as the more fertile group did in 8 months? The answer is 24 months. It is too simplistic to assume that in the current
1580
Penzias
Subfertility and fecundability
study, surgery raised the fecundability from 5.7% to 16.5%, because spontaneous conception and repeat IVF successes have been amalgamated in this mathematical exercise. Comparing fecundability, however, is more than just a mathematical exercise, it can be a useful clinical tool. Returning to the example that I presented earlier, my goal is to give the subfertile couple perspective on their chance of conception relative to the general population. Using the fecundability of 20% in the general population and 1%–3% in the subfertile population as my guide, I tell the couple that it may take subfertile couples 24 months to achieve what the general population achieves in 1 to 3 months (Fig. 1). In the world of infertility treatment 24 months or 2 years has vastly different implications if the female partner of the couple you are speaking to is 42 years old and not 32 years old. Nonetheless, use of fecundability allows direct comparisons of treatments and helps level the playing field when the clinician is faced with multiple therapeutic options. Does laparoscopic treatment of endometriosis improve the outcome of patients undergoing IVF? There are studies in the literature that lean in favor and against the proposition (4, 5). One fact is clear, however: Failure to achieve pregnancy after 1 or 2 cycles of IVF does not mean that pregnancy is not possible for a substantial number of patients. REFERENCES 1. Penzias AS, DeCherney AH. Is there a role for tubal surgery? Am J Obstet Gynecol 1996;174:1218 –23. 2. Littman E, Giudice L, Lathi R, Berker B, Milki A, Nezhat C. Role of laparoscopic treatment of endometriosis in patients who have failed in vitro fertilization cycles. Fertil Steril 2005;84:1574 – 8. 3. Collins JA, Wrixon W, Janes LB, Wilson EH. Treatment-independent pregnancy among infertile couples. N Engl J Med 1983;309:1201– 6. 4. Wong BC, Gillman NC, Oehninger S, Gibbons WE, Stadtmauer LA. Results of in vitro fertilization in patients with endometriomas: is surgical removal beneficial? Am J Obstet Gynecol 2004;191:597– 606. 5. Garcia-Velasco JA, Mahutte NG, Corona J, Zuniga V, Giles J, Arici A, Pellicer A. Removal of endometriomas before in vitro fertilization does not improve fertility outcomes: a matched, case-control study. Fertil Steril 2004;81:1194 –7.
Vol. 84, No. 6, December 2005
Confusion is common when trying to compare the outcome of different fertility treatments. Calculation of fecundability is an excellent adjunct to reports that show cumulative conception totals after a period of observation or treatment. (Fertil Steril威 2005;84:1579 – 80. ©2005 by American Society for Reproductive Medicine.) Key Words: Fecundability, infertility, subfertility, in vitro fertilization
When the infertility evaluation came back “negative”— normal cycle day 3 hormone values, normal hysterosalpingogram, and normal semen analysis—the couple facing me across the desk did not seem all that reassured. She was 32 years old, ovulated regularly, and had an entirely unremarkable menstrual and medical history. He was 35 with no history of paternity and had an equally unremarkable medical history. Their disappointment to my news was understandable; after all, they had spent the better part of 2 years trying to get pregnant and they were hoping for a definitive answer. Puzzled looks followed as I explained that they were not infertile but simply suffered from subfertility. Put another way, they have a calculable chance of becoming pregnant every month but they are among a population likely to conceive at 1%–3% per month rather than 20% per cycle as seen in the general population (1). Fecundability is the chance of becoming pregnant per menstrual cycle. It’s perhaps the single most important statistic available to patients and practitioners, because it allows a head-to-head comparison of treatments. The medical literature is replete with good studies that dutifully report the cumulative percentage of patients who achieve pregnancy over a given period of time following a specified intervention. Relatively few studies, however, calculate the fecundability of the treatment population. For example, consider the following two hypothetical examples. 1) Following administration of fertility drug Omega, 67.2% of the test population conceived during the Received March 27, 2005; revised and accepted March 31, 2005. Reprint requests: Alan S. Penzias, M.D., Boston IVF, 40 Second Avenue, Suite 300, Waltham, Massachusetts 02451 (E-mail: alan.penzias@ bostonivf.com).
0015-0282/05/$30.00 doi:10.1016/j.fertnstert.2005.03.088
18 months of follow-up. 2) Following administration of fertility drug Epsilon, 77.4% of the subjects conceived within 2 years of treatment. The reader of these two studies would be hard pressed to see the treatments as equivalent, though their fecundabilies are both exactly 6%. The study in this month’s journal (2) reports a 76% conception rate (22 of 29) in a population of infertile endometriosis patients who underwent laparoscopy after having failed at least 1 cycle of IVF. The time to conception in 14 of the 22 ranged from 1 to 8 months. A similar group of patients who declined laparoscopy was used as a control population. Among those who did not have laparoscopic treatment of endometriosis, 37% conceived (13 of 35). The very reasonable cumulative conception rate in the control population should not come as a surprise. Collins et al. (3) reported on the incidence of treatment-independent pregnancy in a population of infertility patients followed for 2 to 7 years. A total of 191 of 548 untreated couples (35%) became pregnant. Furthermore, 31% of the pregnancies that occurred in treated couples were achieved 3 months after the last medical treatment or more than 12 months after adnexal surgery. In the present study the distinction between treatmentindependent and treatment-dependent pregnancy is less clear. Of the 22 patients who conceived after undergoing laparoscopic treatment for endometriosis, 12 conceived spontaneously, 2 conceived with clomid and IUI, and 8 conceived with additional IVF treatment. Time to conception data is presented for the 14 nonrepeat IVF pregnancies: 1 to 8 months. Putting aside the method used to achieve pregnancy, hypothetically if all 29 patients who underwent laparoscopy began trying to get pregnant at the same time point postop-
Fertility and Sterility姞 Vol. 84, No. 6, December 2005 Copyright ©2005 American Society for Reproductive Medicine, Published by Elsevier Inc.
1579
FIGURE 1 Cumulative percentage of population pregnant over time as a function of conception rate.
Fecundability Table
Month 1 3 6 12 18 24
Rate 20%
10%
3%
1%
20% 49%
10% 27%
3% 9%
1% 3%
74% 93% 98% 99%
47% 72% 85% 92%
17% 31% 42% 52%
6% 11% 17% 21%
Penzias. Subfertility and fecundability. Fertil Steril 2005.
eratively and 22 of them (76%) were pregnant after 8 months of attempts, the fecundability calculates to 16.5%. Stated another way, if a population of patients has a conception rate of 16.5% per month, 76% of that group will be pregnant by the end of 8 months of attempts. Using the same method to calculate the fecundability of the untreated population, and assuming that all 13 of the 35 patients in that group also conceived by the end of 8 months, the result is 5.7%. Restated, if a population of patients has a conception rate of 5.7% per month, 37% of that group will be pregnant by the end of 8 months of attempts. With comparative fecundability rates of 16.5% and 5.7%, one can then ask how long it should take the less fertile group to achieve the same 76% cumulative pregnancies as the more fertile group did in 8 months? The answer is 24 months. It is too simplistic to assume that in the current
1580
Penzias
Subfertility and fecundability
study, surgery raised the fecundability from 5.7% to 16.5%, because spontaneous conception and repeat IVF successes have been amalgamated in this mathematical exercise. Comparing fecundability, however, is more than just a mathematical exercise, it can be a useful clinical tool. Returning to the example that I presented earlier, my goal is to give the subfertile couple perspective on their chance of conception relative to the general population. Using the fecundability of 20% in the general population and 1%–3% in the subfertile population as my guide, I tell the couple that it may take subfertile couples 24 months to achieve what the general population achieves in 1 to 3 months (Fig. 1). In the world of infertility treatment 24 months or 2 years has vastly different implications if the female partner of the couple you are speaking to is 42 years old and not 32 years old. Nonetheless, use of fecundability allows direct comparisons of treatments and helps level the playing field when the clinician is faced with multiple therapeutic options. Does laparoscopic treatment of endometriosis improve the outcome of patients undergoing IVF? There are studies in the literature that lean in favor and against the proposition (4, 5). One fact is clear, however: Failure to achieve pregnancy after 1 or 2 cycles of IVF does not mean that pregnancy is not possible for a substantial number of patients. REFERENCES 1. Penzias AS, DeCherney AH. Is there a role for tubal surgery? Am J Obstet Gynecol 1996;174:1218 –23. 2. Littman E, Giudice L, Lathi R, Berker B, Milki A, Nezhat C. Role of laparoscopic treatment of endometriosis in patients who have failed in vitro fertilization cycles. Fertil Steril 2005;84:1574 – 8. 3. Collins JA, Wrixon W, Janes LB, Wilson EH. Treatment-independent pregnancy among infertile couples. N Engl J Med 1983;309:1201– 6. 4. Wong BC, Gillman NC, Oehninger S, Gibbons WE, Stadtmauer LA. Results of in vitro fertilization in patients with endometriomas: is surgical removal beneficial? Am J Obstet Gynecol 2004;191:597– 606. 5. Garcia-Velasco JA, Mahutte NG, Corona J, Zuniga V, Giles J, Arici A, Pellicer A. Removal of endometriomas before in vitro fertilization does not improve fertility outcomes: a matched, case-control study. Fertil Steril 2004;81:1194 –7.
Vol. 84, No. 6, December 2005