- Email: [email protected]
Location of semen collection and time interval from collection to use for intrauterine insemination
Location of semen collection and time interval from collection to use for intrauterine insemination The location of semen collection (home vs. clinic) for IUI did not affect pregnancy rates in a general infertility population (633 IUI cycles from 335 patients), if World Health Organization guidelines for time from specimen collection to use were followed. The time interval from semen collection to IUI was not different between patients who conceived and those who did not (pregnant vs. nonpregnant, 70 19 minutes vs. 73 18 minutes). (Fertil Steril 2007;88:1689–91. 2007 by American Society for Reproductive Medicine.)
Intrauterine insemination (IUI) is an effective treatment for various forms of infertility. Several investigators have studied the indications and protocols for ovulation induction and the methodology for the semen preparation (1–3). However, a number of questions remain unanswered, including whether the location of semen collection affects semen quality or the chance of pregnancy, and how well sperm withstand exposure to seminal plasma or media for >30 minutes before insemination. In a retrospective study of 62 couples undergoing IUI, Yavas and Selub (4) found that semen collection at home resulted in a pregnancy rate that was roughly half of the rate for patients who collected in the clinic among gonadotropin-treated patients, and that interval of >30 minutes between semen collection and sperm wash reduced pregnancy rates. However, there was no difference in pregnancy rates with time interval or place of collection if the woman was treated with clomiphene citrate. The Yavas study was limited by a relatively small population (11 to 69 cycles per treatment group). The goal of our study was to determine whether the place of semen collection or the time interval from semen collection to IUI affects the pregnancy rates in a larger population. We hypothesized that the pregnancy rate with semen collection in clinic would be 17%, which would represent a 100% increase from the historical average pregnancy rate (8.5%) in our center, based on the difference seen in the Yavas and Selub (4) report. With a power of 80%, we would require at least 219 cycles per group to detect this difference assuming a significance level of 0.05. We analyzed the outcomes for a total of 633 IUI cycles (clinic collection: 397 cycles; home collection: 236 cycles), treated during the period June 2005 to January 2006 after approval from Research Subjects Review Board at the University of Rochester. Received October 4, 2006; revised and accepted January 11, 2007. Conflict of interest: Gyun Jee Song: none; Rita Herko: none; Vivian Lewis: Wyeth Ayerst Research M and Glaxo Smith Kline M. Reprint requests: Vivian Lewis, M.D., 601 Elmwood Avenue, Box 668, University of Rochester Medical Center, Rochester, New York 14642 (FAX: 585-756-5717; E-mail: [email protected]. edu).
0015-0282/07/$32.00 doi:10.1016/j.fertnstert.2007.01.051
Women with infertility underwent IUI if they had at least one normal, patent fallopian tube ipsilateral to a functioning ovary. Intrauterine insemination was performed without ovulation induction in 69 cycles of infertility because of cervical factor or male factor (primarily to reduce risk of multiple birth, but also for patient preference). We used clomiphene citrate or gonadotropins (recombinant FSH or menopausal gonadotropins) to induce ovulation, as previously described, performing IUI on the day after the onset of a naturally occurring LH surge or 33–40 hours after hCG administration (5, 6). All patients were instructed to have a serum pregnancy test 14 days after the IUI. Patients with positive pregnancy tests were followed with serial hCG levels. Ongoing pregnancies were defined as those in which there was ultrasound visualization of a fetal pole with cardiac activity at 6–7 weeks of gestation. Patients were given the option of bringing the semen sample from home, if travel time was expected to be <45 minutes in accordance to World Health Organization (WHO) guidelines, which recommend that the sample should be collected in a private room near the laboratory. If this is not possible, the sample should be delivered to the laboratory within 1 hour of collection. In our center, we recommend a maximum 45-minute interval from collection to delivery of the samples to the laboratory, and that the sample be kept close to body temperature. We recorded the time of semen collection, start and completion of sperm wash, and insemination time, as well as the place of semen collection (home vs. clinic). After semen collection in the clinic, the specimen was kept at 36 C on the slide warmer, and processing was started within 15 to 30 minutes. In the case of semen collection outside of clinic, semen processing was started as soon as the sample was received in the clinic. Using a density gradient centrifugation procedure, the motile sperm were separated from white blood cells and debris. After sperm washing, sperm count and motility were measured again. The sperm pellet was suspended in 0.3–0.5 mL of medium and the sample placed on a slide warmer (36 C) until the female patient was ready. All statistical analyses were performed with SPSS computer software (SPSS Inc., Chicago, IL). For comparison between groups, we used
Fertility and Sterility Vol. 88, No. 6, December 2007 Copyright ª2007 American Society for Reproductive Medicine, Published by Elsevier Inc.
1689
the Student t test, one-way analysis of variance and the chisquare test. The etiologies of infertility were similar among the patients who collected at home and those who collected in the clinic, including the proportion of men with abnormal semen analysis (23% vs. 20% in clinic vs. home, P¼.14). Thirty-four percent of patients were treated with gonadotropins, which was a similar proportion in both groups (33% vs. 36% in clinic vs. home, P¼.6). There was no difference between groups in the percentage of patients treated with clomiphene citrate. We first compared the pregnancy rate for patients with semen collection in clinic to semen collection at home. There was no significant difference between the ongoing pregnancy rates in the two groups (Table 1). As we expected, the time interval from semen collection to sperm wash or insemination was shorter for the group that collected in the clinic. Nonetheless, semen parameters including motility and pregnancy rate were not significantly better. Next, we compared the cycles resulting in pregnancy to cycles that failed, with respect to the average time intervals from semen collection to sperm wash and insemination (Table 1). There was no significant difference in time intervals or semen parameters including sperm count and motility. We also compared the pregnancy rate between short and longer exposure of sperm to seminal plasma before insemination. We observed no difference in the pregnancy rate between short time (<30 minutes) and longer time intervals (30 to 60 minutes). None of the seven cycles of IUI in which exposure exceeded 1 hour resulted in pregnancy (P>.05).
We did the same analyses in the subgroup of patients (n ¼ 116 cycles) with lower sperm motility (<25%), because sperm samples with poor motility would be more likely to be damaged by the delay caused by transport to the clinic. The pregnancy rates of home and clinic collection groups were 6.8% versus 7.1%, (P>.05). We observed no difference in pregnancy rates of home-collected versus clinic-collected samples for patients with male factor (e.g., abnormalities in any semen parameter according to WHO guidelines). Transport temperature is possibly important, so we compared the pregnancy rate of summer (June–August) and winter (November–January) cycles in the home-collection group. We did not see a significant difference in pregnancy rates (home in summer vs. home in winter; 13.9% (6 of 43) vs. 10.6% (12 of 113), P¼.23). Our hypothesis was that prolonged exposure of sperm to seminal plasma would have harmful effects on IUI cycle outcome. However, we found that the time interval from semen collection to IUI was not a factor in determining pregnancy rates if we followed WHO recommendations (7). Laboratory staff and nurses emphasize the importance of time interval from collection to sperm washing when counseling patients. The average time from collection to sperm wash in the home collection group was 29 minutes, and only 2.9% (7 of 236) of cycles were over the 60-minute interval from collection to sperm washing. We found that home collection had no harmful effect on pregnancy rates, even though the average time from collection to sperm washing was significantly longer among
TABLE 1 Semen values and time intervals from semen collection to insemination of intrauterine insemination (IUI) cycles (mean ± SD) in the groups with clinic versus home collection of semen or in the pregnant versus nonpregnant groups. Collection place
Age of female patient (years) Semen parameters Sperm count (million/mL) Sperm motility (%) Progressive (velocity) Total motile sperm (million) Time intervals (min) Collection to washing Washing to insemination Collection to insemination Ongoing pregnancy rate a
Pregnancy
Clinic (n [ 397)
Home (n [ 236)
Pregnant (n [ 88)
Nonpregnant (n [ 545)
34 4.3
35 4.9a
34 4.7
34 4.9
59 40 44 19 31 7 81 84
58 40 41 17 30 7a 67 73
65 43 45 20 32 7 88 93
58 40 43 18 30 7 71 75
20 11 18 12 70 19
20 13 20 13 73 18
14 8 21 14 69 15 7.3% (29/397)
29 15a 18 11a 81 20a 10.6% (25/236)
P value < .05; n ¼ the number of cycles.
Song. Semen collection time and location for IUI. Fertil Steril 2007.
1690
Song et al.
Correspondence
Vol. 88, No. 6, December 2007
patients who collected at home compared with those who collected at the clinic (29 vs. 14 minutes). Our results differ from those of Yavas and Selub (4), who recommended that semen be collected at the clinic and processed within 30 minutes of collection to maximize pregnancy rates. Based on our findings in a larger population, home collection can be recommended if patients can comply with WHO guidelines. Gyun Jee Song, Ph.D. Rita Herko, B.S. Vivian Lewis, M.D. Department of Obstetric and Gynecology, University of Rochester Medical Center, Rochester, New York REFERENCES 1. Karlstrom PO, Bakos O, Bergh T, Lundkvist O. Intrauterine insemination and comparison of two methods of sperm preparation. Hum Reprod 1991;6:390–5.
Fertility and Sterility
2. Mahani IM, Afnan M. The pregnancy rates with intrauterine insemination (IUI) in superovulated cycles employing different protocols (clomiphen citrate (CC), human menopausal gonadotropin (HMG) and HMGþCC) and in natural ovulatory cycle. J Pak Med Assoc 2004;54: 503–5. 3. Gomez-Palomares JL, Julia B, Acevedo-Martin B, Martinez-Burgos M, Hernandez ER, Ricciarelli E. Timing ovulation for intrauterine insemination with a GnRH antagonist. Hum Reprod 2005;20:368–72. 4. Yavas Y, Selub MR. Intrauterine insemination (IUI) pregnancy outcome is enhanced by shorter intervals from semen collection to sperm wash, from sperm wash to IUI time, and from semen collection to IUI time. Fertil Steril 2004;82:1638–47. 5. Guzick DS, Carson SA, Coutifaris C, Overstreet JW, Factor-Litvak P, Steinkampf MP, et al. Efficacy of superovulation and intrauterine insemination in the treatment of infertility. National Cooperative Reproductive Medicine Network [see comment]. N Engl J Med 1999;340: 177–83. 6. Lewis V, Queenan Jr J, Hoeger K, Stevens J, Guzick DS. Clomiphene citrate monitoring for intrauterine insemination timing: a randomized trial. Fertil Steril 2006;85:401–6. 7. WHO. Laboratory manual for the examination of human semen and sperm-cervical mucus interaction. New York: Cambridge University Press, 1999.
1691
Intrauterine insemination (IUI) is an effective treatment for various forms of infertility. Several investigators have studied the indications and protocols for ovulation induction and the methodology for the semen preparation (1–3). However, a number of questions remain unanswered, including whether the location of semen collection affects semen quality or the chance of pregnancy, and how well sperm withstand exposure to seminal plasma or media for >30 minutes before insemination. In a retrospective study of 62 couples undergoing IUI, Yavas and Selub (4) found that semen collection at home resulted in a pregnancy rate that was roughly half of the rate for patients who collected in the clinic among gonadotropin-treated patients, and that interval of >30 minutes between semen collection and sperm wash reduced pregnancy rates. However, there was no difference in pregnancy rates with time interval or place of collection if the woman was treated with clomiphene citrate. The Yavas study was limited by a relatively small population (11 to 69 cycles per treatment group). The goal of our study was to determine whether the place of semen collection or the time interval from semen collection to IUI affects the pregnancy rates in a larger population. We hypothesized that the pregnancy rate with semen collection in clinic would be 17%, which would represent a 100% increase from the historical average pregnancy rate (8.5%) in our center, based on the difference seen in the Yavas and Selub (4) report. With a power of 80%, we would require at least 219 cycles per group to detect this difference assuming a significance level of 0.05. We analyzed the outcomes for a total of 633 IUI cycles (clinic collection: 397 cycles; home collection: 236 cycles), treated during the period June 2005 to January 2006 after approval from Research Subjects Review Board at the University of Rochester. Received October 4, 2006; revised and accepted January 11, 2007. Conflict of interest: Gyun Jee Song: none; Rita Herko: none; Vivian Lewis: Wyeth Ayerst Research M and Glaxo Smith Kline M. Reprint requests: Vivian Lewis, M.D., 601 Elmwood Avenue, Box 668, University of Rochester Medical Center, Rochester, New York 14642 (FAX: 585-756-5717; E-mail: [email protected]. edu).
0015-0282/07/$32.00 doi:10.1016/j.fertnstert.2007.01.051
Women with infertility underwent IUI if they had at least one normal, patent fallopian tube ipsilateral to a functioning ovary. Intrauterine insemination was performed without ovulation induction in 69 cycles of infertility because of cervical factor or male factor (primarily to reduce risk of multiple birth, but also for patient preference). We used clomiphene citrate or gonadotropins (recombinant FSH or menopausal gonadotropins) to induce ovulation, as previously described, performing IUI on the day after the onset of a naturally occurring LH surge or 33–40 hours after hCG administration (5, 6). All patients were instructed to have a serum pregnancy test 14 days after the IUI. Patients with positive pregnancy tests were followed with serial hCG levels. Ongoing pregnancies were defined as those in which there was ultrasound visualization of a fetal pole with cardiac activity at 6–7 weeks of gestation. Patients were given the option of bringing the semen sample from home, if travel time was expected to be <45 minutes in accordance to World Health Organization (WHO) guidelines, which recommend that the sample should be collected in a private room near the laboratory. If this is not possible, the sample should be delivered to the laboratory within 1 hour of collection. In our center, we recommend a maximum 45-minute interval from collection to delivery of the samples to the laboratory, and that the sample be kept close to body temperature. We recorded the time of semen collection, start and completion of sperm wash, and insemination time, as well as the place of semen collection (home vs. clinic). After semen collection in the clinic, the specimen was kept at 36 C on the slide warmer, and processing was started within 15 to 30 minutes. In the case of semen collection outside of clinic, semen processing was started as soon as the sample was received in the clinic. Using a density gradient centrifugation procedure, the motile sperm were separated from white blood cells and debris. After sperm washing, sperm count and motility were measured again. The sperm pellet was suspended in 0.3–0.5 mL of medium and the sample placed on a slide warmer (36 C) until the female patient was ready. All statistical analyses were performed with SPSS computer software (SPSS Inc., Chicago, IL). For comparison between groups, we used
Fertility and Sterility Vol. 88, No. 6, December 2007 Copyright ª2007 American Society for Reproductive Medicine, Published by Elsevier Inc.
1689
the Student t test, one-way analysis of variance and the chisquare test. The etiologies of infertility were similar among the patients who collected at home and those who collected in the clinic, including the proportion of men with abnormal semen analysis (23% vs. 20% in clinic vs. home, P¼.14). Thirty-four percent of patients were treated with gonadotropins, which was a similar proportion in both groups (33% vs. 36% in clinic vs. home, P¼.6). There was no difference between groups in the percentage of patients treated with clomiphene citrate. We first compared the pregnancy rate for patients with semen collection in clinic to semen collection at home. There was no significant difference between the ongoing pregnancy rates in the two groups (Table 1). As we expected, the time interval from semen collection to sperm wash or insemination was shorter for the group that collected in the clinic. Nonetheless, semen parameters including motility and pregnancy rate were not significantly better. Next, we compared the cycles resulting in pregnancy to cycles that failed, with respect to the average time intervals from semen collection to sperm wash and insemination (Table 1). There was no significant difference in time intervals or semen parameters including sperm count and motility. We also compared the pregnancy rate between short and longer exposure of sperm to seminal plasma before insemination. We observed no difference in the pregnancy rate between short time (<30 minutes) and longer time intervals (30 to 60 minutes). None of the seven cycles of IUI in which exposure exceeded 1 hour resulted in pregnancy (P>.05).
We did the same analyses in the subgroup of patients (n ¼ 116 cycles) with lower sperm motility (<25%), because sperm samples with poor motility would be more likely to be damaged by the delay caused by transport to the clinic. The pregnancy rates of home and clinic collection groups were 6.8% versus 7.1%, (P>.05). We observed no difference in pregnancy rates of home-collected versus clinic-collected samples for patients with male factor (e.g., abnormalities in any semen parameter according to WHO guidelines). Transport temperature is possibly important, so we compared the pregnancy rate of summer (June–August) and winter (November–January) cycles in the home-collection group. We did not see a significant difference in pregnancy rates (home in summer vs. home in winter; 13.9% (6 of 43) vs. 10.6% (12 of 113), P¼.23). Our hypothesis was that prolonged exposure of sperm to seminal plasma would have harmful effects on IUI cycle outcome. However, we found that the time interval from semen collection to IUI was not a factor in determining pregnancy rates if we followed WHO recommendations (7). Laboratory staff and nurses emphasize the importance of time interval from collection to sperm washing when counseling patients. The average time from collection to sperm wash in the home collection group was 29 minutes, and only 2.9% (7 of 236) of cycles were over the 60-minute interval from collection to sperm washing. We found that home collection had no harmful effect on pregnancy rates, even though the average time from collection to sperm washing was significantly longer among
TABLE 1 Semen values and time intervals from semen collection to insemination of intrauterine insemination (IUI) cycles (mean ± SD) in the groups with clinic versus home collection of semen or in the pregnant versus nonpregnant groups. Collection place
Age of female patient (years) Semen parameters Sperm count (million/mL) Sperm motility (%) Progressive (velocity) Total motile sperm (million) Time intervals (min) Collection to washing Washing to insemination Collection to insemination Ongoing pregnancy rate a
Pregnancy
Clinic (n [ 397)
Home (n [ 236)
Pregnant (n [ 88)
Nonpregnant (n [ 545)
34 4.3
35 4.9a
34 4.7
34 4.9
59 40 44 19 31 7 81 84
58 40 41 17 30 7a 67 73
65 43 45 20 32 7 88 93
58 40 43 18 30 7 71 75
20 11 18 12 70 19
20 13 20 13 73 18
14 8 21 14 69 15 7.3% (29/397)
29 15a 18 11a 81 20a 10.6% (25/236)
P value < .05; n ¼ the number of cycles.
Song. Semen collection time and location for IUI. Fertil Steril 2007.
1690
Song et al.
Correspondence
Vol. 88, No. 6, December 2007
patients who collected at home compared with those who collected at the clinic (29 vs. 14 minutes). Our results differ from those of Yavas and Selub (4), who recommended that semen be collected at the clinic and processed within 30 minutes of collection to maximize pregnancy rates. Based on our findings in a larger population, home collection can be recommended if patients can comply with WHO guidelines. Gyun Jee Song, Ph.D. Rita Herko, B.S. Vivian Lewis, M.D. Department of Obstetric and Gynecology, University of Rochester Medical Center, Rochester, New York REFERENCES 1. Karlstrom PO, Bakos O, Bergh T, Lundkvist O. Intrauterine insemination and comparison of two methods of sperm preparation. Hum Reprod 1991;6:390–5.
Fertility and Sterility
2. Mahani IM, Afnan M. The pregnancy rates with intrauterine insemination (IUI) in superovulated cycles employing different protocols (clomiphen citrate (CC), human menopausal gonadotropin (HMG) and HMGþCC) and in natural ovulatory cycle. J Pak Med Assoc 2004;54: 503–5. 3. Gomez-Palomares JL, Julia B, Acevedo-Martin B, Martinez-Burgos M, Hernandez ER, Ricciarelli E. Timing ovulation for intrauterine insemination with a GnRH antagonist. Hum Reprod 2005;20:368–72. 4. Yavas Y, Selub MR. Intrauterine insemination (IUI) pregnancy outcome is enhanced by shorter intervals from semen collection to sperm wash, from sperm wash to IUI time, and from semen collection to IUI time. Fertil Steril 2004;82:1638–47. 5. Guzick DS, Carson SA, Coutifaris C, Overstreet JW, Factor-Litvak P, Steinkampf MP, et al. Efficacy of superovulation and intrauterine insemination in the treatment of infertility. National Cooperative Reproductive Medicine Network [see comment]. N Engl J Med 1999;340: 177–83. 6. Lewis V, Queenan Jr J, Hoeger K, Stevens J, Guzick DS. Clomiphene citrate monitoring for intrauterine insemination timing: a randomized trial. Fertil Steril 2006;85:401–6. 7. WHO. Laboratory manual for the examination of human semen and sperm-cervical mucus interaction. New York: Cambridge University Press, 1999.
1691