Vol. 55, No.2, February 1991
FERTILITY AND STERILITY
Printed on acid-free paper in U.S.A.
Copyright 1991 The American Fertility Society
A comparative analysis of the cycle fecundity rates associated with combined human menopausal gonadotropin (hMG) and intrauterine insemination (lUI) versus either hMG or lUI alone*
Linda M. Chafi'kin, M.D. John C. Nulsen, M.D. Anthony A. Luciano, M.D. Deborah A. Metzger, Ph.D., M.D.t Division of Reproductive Endocrinology and Infertility, Depart';ent of Obstetrics and Gynecology, University of Connecticut Health Center, Farmington, Connecticut
Human menopausal gonadotropin (hMG) superovulation combined with washed intrauterine insemination (lUI) has been advocated for the treatment of various forms of infertility when more traditional therapy has failed. To assess the relative efficacy of combined treatment with hMG and lUI compared with either hMG or lUI alone, pregnancy outcomes of the three treatment groups were compared in couples having infertility because of male factor, cervical factor, endometriosis, or unexplained. A total of 751 cycles were analyzed from 322 couples. The mean cycle fecundity rate associated with hMG/IUI therapy was significantly higher than either hMG or lUI therapy alone for all patients (hMG/IUI = 19.6%, hMG = 6.3%, lUI = 3.4%). The improvement in cycle fecundity rates with hMG/IUI therapy was also observed when the couples were separated by infertility diagnostic groups: male factor (hMG/IUI = 15.3%, hMG = 4.4%, lUI = 3.0%), cervical factor (hMG/IUI = 26.3%, hMG = 7.9%, lUI = 5.1%), endometriosis (hMG/IUI = 12.85%, hMG = 6.6%), and unexplained infertility (hMG/IUI = 32.6%, hMG = 5.5%, lUI = 0%). Moreover, in patients who had failed to conceive with hMG or lUI alone, the cycle fecundity rate when they were switched to hMG/IUI therapy equaled that of patients who received combined therapy from the onset. We conclude that cycle fecundity rates and cumulative pregnancy rates are significantly greater using a combination ofhMG and lUI compared with either modality alone in the treatment of male factor, cervical factor, endometriosis, or unexplained infertility. Indeed, in couples with nontubal related infertility, cycle fecundity rates with hMG/IUI approach the rates seen with in vitro fertilization and gamete intrafallopian tube transfer. Fertil Steril55:252, 1991
The combined therapy of controlled superovulation with human menopausal gonadotropins (hMG) and intrauterine insemination (lUI) has recently been introduced as an effective method of treating infertile couples with patent fallopian tubes when more traditional therapy has failed. 1,2
Received April 24, 1990; revised and accepted October 4, 1990. * Presented in part at the 45th Annual Meeting of The American Fertility Society, San Francisco, California, November 13 to 16, 1989. t Reprint requests: Deborah A. Metzger, M.D., Ph.D., Department of Reproductive Endocrinology, University of Connecticut Health Center, Farmington, Connecticut 06030.
252
Chaff'kin et al.
Although the efficacy of the combined treatment has been demonstrated to be superior to hMG or lUI alone in unexplained infertility,3 the relative efficacy of hMG, lUI, and hMGjlUI has not been adequately defined for other causes of infertility. A comparison of the cycle fecundity rate for hMGj lUI versus that associated with the use of hMG or lUI alone would provide the basis for assessment of whether the relative chances of pregnancy justify the increased cost and may help us define the best treatment for each of the various infertility diagnoses. Thus, we performed this retrospective study to evaluate the hypothesis that the cycle fecundity rate is improved with controlled hMG superovulation combined with lUI. In addition, we
Combined hMGjIUI versus hMG or lUI alone
Fertility and Sterility
also evaluated the efficacy of superovulation in conjunction with lUI in patients who had previously failed either hMG or lUI alone. MATERIALS AND METHODS
The records of 322 patients who had been treated with lUI, controlled hMG superovulation, or hMG combined with lUI (hMG/IUI) during 1986 to 1989 at the University of Connecticut Health Center were reviewed retrospectively. Before treatment, all couples underwent a complete infertility evaluation that included ovulation assessment by basal body temperature (BBT) recording and endometrial biopsy, postcoital test (PCT), hysterosalpingogram (HSG), semen analysis, and, in the majority of cases, diagnostic laparoscopy. We excluded couples in whom anovulation was the sole documented cause of infertility. Patients were grouped according to infertility diagnosis. When multiple factors were present, each factor was separately tabulated. Infertility subgroups were defined as follows: (1) male factor in which two or more semen analyses obtained at least 1 month apart revealed a sperm density < 20 X 106 sperm/mL and/or
20
E
0
Do
-• c c
~ A
0
• -; ::I
0
1
0
100
2
5
4
3
0
8
0
2
3
4
Cycle number
HMG
Figure 3 Cumulative PRs with combined hMG/IUI therapy in patients who previously failed either lUI or hMG therapy.
80
C
o t:o
80
!! A
40
was similar to that of patients who received hMG in combination with lUI from the onset (Fig. 3).
I
20
DISCUSSION
A
i::a
E
0
::a
0
U
100
2
1
3
4
3
4
5
8
HMG/IUI
80 80
40 20
2
5
6
Cycle Figure 2 Cumulative PRs by therapeutic groups (lUI, hMG, or hMG/IUI) with each infertility factor examined separately.
(cycle fecundity 14%). The cumulative PR after the initiation of hMGjIUI therapy in these treatment failure groups (58% after 4 cycles oftherapy) Table 2
Cycle Fecundity Rates by Cycle Number"
Cycle number
lUI
HMG
HMG/1U1
1 2 3 4
4.5 5.8 0.0 4.0 5.8
4.3 7.1 7.5 9.5 7.6
19.0 18.5 25.5 9.4 2.8
5 " Values are percents.
Vol. 55, No.2, February 1991
Intrauterine insemination has been employed for many years in the treatment of the infertile couple. Success rates with male factor and unexplained infertility have generally been discouraging,3,5-14 although patients with cervical factor infertility appear to fare somewhat betterp-21 A literature review by Allen et al. 19 noted an overall PR of 25% for lUI-treated male factor infertility (range 7%12 to 66%13) and 60% for cervical factor infertility (range 52%16 to 70%13). The mean overall PR reported was 28% (range 3.4%20 to 62.0%13), similar to our results in the lUI alone group. Although hMG has been recently advocated21 for the treatment of ovulatory women with longstanding idiopathic infertility, improvement in cycle fecundity in ovulatory women with male factor infertility, cervical factor infertility, or endometriosis has not been demonstrated when hMG is used alone. Our results suggest that hMG alone is of minimal therapeutic benefit when compared with the cycle fecundity and cumulative PRs associated with combined hMGjIUI therapy. Considering the expense and risks involved with controlled hMG superovulation therapy, it is logical to maximize the benefits to the patient by the addition of lUI. The results of our experience with hMG combined with lUI are very encouraging and similar to those reported by other investigators, although a direct comparison of cycle fecundity with hMG, lUI, and hMGjIUI has not been previously reported. Recently, Dodson and colleagues1 reported a cycle fecundity with hMG JIUI therapy of 29% for
Chaffkin et al.
Combined hMG/IUI versus hMG or lUI alone
255
cervical factor, 17% for endometriosis, and 19% for idiopathic infertility. Couples with abnormalities in semen analysis were excluded from this study. Serhal et a1. 3 reported a cycle fecundity rate of 26.4% with hMG/IUI in the treatment of unexplained infertility and noted this to represent a 10fold increase when compared with patients who received lUI alone. Corson et a1. 2 reported a statistically significant increase in cycle fecundity rate (from 5% to 11%) with hMG/IUI treatment as compared with lUI alone in patients who had cervical factor abnormalities. Our results confirm the therapeutic efficacy of the combined hMG/IUI therapy as reported in these studies and suggest that the combined therapy is much more effective than either lUI or hMG alone for all infertility factors studied. Attempts at improving PRs with infertility associated with endometriosis have been somewhat discouraging. Recent controlled studies demonstrate no enhancement of fertility after medical therapy with both treated and expectantly managed groups having cycle fecundity rates between 2% and 6%.22 Although women with mild and moderate endometriosis fare as well with in vitro fertilization (IVF) as women with tubal factor infertility,20 there are no less invasive procedures with demonstrated efficacy in enhancing fertility in endometriosis. The results of this study are significant for two reasons: (1) all of the women in the study had undergone laparoscopic laser surgery as initial treatment for their endometriosis and failed to conceive 6 to 24 months after treatment. Thus, these patients represent a group of treatment failures, and (2) the cycle fecundity rates observed with combined hMG/IUI are two to six times higher than reported with expectant management or hormonal therapy and two times that observed with hMG alone. Thus, these results suggest that combined hMG/ lUI therapy may be an effective alternative to IVF for the treatment of infertility associated with endometriosis. Several factors can account for the dramatic improvement in cycle fecundity with hMG/IUI therapy, regardless of the apparent etiology of infertility. The number and concentration of sperm in the upper genital tract are increased, while simultaneously, a greater number of target oocytes are made available. This may improve chances of fertilization where a gametotoxic effect may be present, as has been suggested for endometriosis-associated infertility.24 Occult ovulatory disturbances may be corrected and barriers to sperm that may 256
Chaffkin et al.
be present in the cervical mucus are bypassed. The procedure also offers the technical benefit of improving the timing of insemination relative to ovulation. The advantages of hMG/IUI are similar in theory to those offered by gamete intrafallopian transfer (GIFT). Both techniques increase the number of male and female gametes present at the site of fertilization. The cycle fecundity rate in our experience is equivalent to that reported for IVF but not quite as good as GIFT.25 However, hMG/IUI therapy avoids the need for general anesthesia, invasive oocyte retrieval, and provides a significant savings in cost. Intensive monitoring, however, is still required to minimize the risks of ovarian hyperstimulation and multiple pregnancy, which must be considered when evaluating this mode of therapy. In conclusion, we found the cycle fecundity rates and cumulative PRs to be significantly greater using a combination ofhMG and lUI when compared with either modality used alone in the treatment of male factor, cervical factor, or unexplained infertility. The increase in cycle fecundity rate in patients with laparoscopic evidence of endometriosis approached, but did not meet, the criteria for statistical significance when comparing hMG/IUI therapy with hMG alone. Human menopausal gonadotropin/lUI appears to be a viable treatment option in patients with infertility refractory to other treatments, or before the institution of IVF/GIFT therapy in patients with patent fallopian tubes.
REFERENCES 1. Dodson WC, Whitesides DB, Hughes CL, Jr, Easley HA
2.
3.
4.
5.
6.
Combined hMGjIUI versus hMG or lUI alone
III, Haney AF: Superovulation with intrauterine insemination in the treatment of infertility: a possible alternative to gamete intrafallopian transfer and in vitro fertilization. Fertil SteriI48:441, 1987 Corson SL, Batzer FR, Gocial B, Maislin G: Intrauterine insemination and ovulation stimulation as treatment of infertility. J Reprod Med 34:397,1989 Serhal PF, Katz M, Little V, Woronowski H: Unexplained infertility-the value Pergonal superovulation combined with intrauterine insemination. Fertil Steril49:602, 1988 Cramer DW, Walker AM, Schiff I: Statistical methods in evaluating the outcome of infertility therapy. Fertil Steril 32:80,1979 Kerin JFP, Peek J, Warnes GM, Kirby C, Jeffrey R, Matthews CD, Cox LW: Improved conception rate after intrauterine insemination of washed spermatozoa from men with poor quality semen. Lancet 1:553, 1984 Hoing L, Devroey P, Van Steirteghem A: Treatment of infertility because of oligoasthenoteratospermia by transcervical intrauterine insemination of motile spermatozoa. Fertil Steril 45:388, 1986
Fertility and Sterility
7. Toffie RC, Nagel TC, Tagatz GE, Phansey SA, Okagaki T, Wavrin CA: Intrauterine insemination: the University of Minnesota experience. Fertil Steril43:743, 1985 8. Hewitt J, Cohen J, Krishnaswamy V, Fehilly CB, Steptoe PC, Walters DE: Treatment of idiopathic infertility, cervical mucus hostility, and male infertility: artificial insemination with husband's semen or in vitro fertilization? Fertil Steril44:350, 1985 9. DiMarzo SJ, Rakofl' JS: Intrauterine insemination with husband's washed sperm. Fertil Steril46:470, 1986 10. Makler A: Washed intrauterine insemination in the treatment of idiopathic infertility. Semin Reprod Endocrinol5: 35, 1987 11. Sher G, Knutzen VK, Stratton CJ, Montakhab MM, Allenson SG: In vitro sperm capacitation and transcervical intrauterine insemination for the treatment of refractory infertility: phase 1. Fertil Steril41:260, 1984 12. Wiltbank MC, Kosasa TS, Rogers BJ: Treatment of infertile patients by intrauterine insemination of washed spermatozoa. Andrologia 17:22, 1985 13. Barwin BN: Intrauterine insemination of husband's semen. J Reprod Fertil36:101, 1974 14. Yovich JL, Matson PL: The treatment of infertility by the high intrauterine insemination of husband's washed spermatozoa. Hum Reprod 3:939, 1988 15. Lalich R, Marut E, Prins G, Scommegna A: Life table analysis of intrauterine insemination pregnancy rates. Am J Obstet GynecoI158:980, 1988 16. Glezerman M, Bernstein D, Insler V: The cervical factor of infertility and intrauterine insemination. Int J Fertil29:16, 1984
Vol. 55, No.2, February 1991
17. Confino E, Friberg J, Dudkiewicz AB, Gleicher N: Intrauterine insemination with washed human spermatozoa. Fertil Steril 46:55, 1986 18. Quagliarello J, Arny M: Intracervical versus intrauterine insemination: correlation of outcome with antecedent postcoital testing. Fertil Steril 46:870, 1986 19. Allen NC, Herbert CM, Maxson WS, Rogers BJ, Diamond MP, Wentz AC: Intrauterine insemination: a critical review. Fertil Steril 44:569, 1985 20. Mastroianni L, Jr, Laberge JL, Rock J: Appraisal of the efficacy of artificial insemination with husband's sperm and evaluation of insemination technics. Fertil Steril 8:260, 1957 21. WeIner S, DeCherney AH, Lake Polan M: Human menopausal gonadotropins: a justifiable therapy in ovulatory women with long-standing idiopathic infertility. Am J Obstet GynecoI158:111, 1988 22. Olive DL, Haney AF: Endometriosis-associated infertility: a critical review of therapeutic approaches. Obstet Gynecol Survey 41:538,1986 23. Matson PL, Yovich JL: The treatment of infertility associated with endometriosis by in vitro fertilization. Fertil SteriI46:432, 1986 24. Syrop CH, Halme J: Peritoneal fluid environment and infertility. Fertil Steril48:1, 1987 25. Medical Research International and the Society for Assisted Reproductive Technology, The American Fertility Society: In vitro fertilization-embryo transfer in the United States: 1988 results from the IVF-ET Registry. Fertil Steril 53:13,1990
Chaffkin et al.
Combined hMG/IUI versus hMG or lUI alone
257
FERTILITY AND STERILITY
Printed on acid-free paper in U.S.A.
Copyright 1991 The American Fertility Society
A comparative analysis of the cycle fecundity rates associated with combined human menopausal gonadotropin (hMG) and intrauterine insemination (lUI) versus either hMG or lUI alone*
Linda M. Chafi'kin, M.D. John C. Nulsen, M.D. Anthony A. Luciano, M.D. Deborah A. Metzger, Ph.D., M.D.t Division of Reproductive Endocrinology and Infertility, Depart';ent of Obstetrics and Gynecology, University of Connecticut Health Center, Farmington, Connecticut
Human menopausal gonadotropin (hMG) superovulation combined with washed intrauterine insemination (lUI) has been advocated for the treatment of various forms of infertility when more traditional therapy has failed. To assess the relative efficacy of combined treatment with hMG and lUI compared with either hMG or lUI alone, pregnancy outcomes of the three treatment groups were compared in couples having infertility because of male factor, cervical factor, endometriosis, or unexplained. A total of 751 cycles were analyzed from 322 couples. The mean cycle fecundity rate associated with hMG/IUI therapy was significantly higher than either hMG or lUI therapy alone for all patients (hMG/IUI = 19.6%, hMG = 6.3%, lUI = 3.4%). The improvement in cycle fecundity rates with hMG/IUI therapy was also observed when the couples were separated by infertility diagnostic groups: male factor (hMG/IUI = 15.3%, hMG = 4.4%, lUI = 3.0%), cervical factor (hMG/IUI = 26.3%, hMG = 7.9%, lUI = 5.1%), endometriosis (hMG/IUI = 12.85%, hMG = 6.6%), and unexplained infertility (hMG/IUI = 32.6%, hMG = 5.5%, lUI = 0%). Moreover, in patients who had failed to conceive with hMG or lUI alone, the cycle fecundity rate when they were switched to hMG/IUI therapy equaled that of patients who received combined therapy from the onset. We conclude that cycle fecundity rates and cumulative pregnancy rates are significantly greater using a combination ofhMG and lUI compared with either modality alone in the treatment of male factor, cervical factor, endometriosis, or unexplained infertility. Indeed, in couples with nontubal related infertility, cycle fecundity rates with hMG/IUI approach the rates seen with in vitro fertilization and gamete intrafallopian tube transfer. Fertil Steril55:252, 1991
The combined therapy of controlled superovulation with human menopausal gonadotropins (hMG) and intrauterine insemination (lUI) has recently been introduced as an effective method of treating infertile couples with patent fallopian tubes when more traditional therapy has failed. 1,2
Received April 24, 1990; revised and accepted October 4, 1990. * Presented in part at the 45th Annual Meeting of The American Fertility Society, San Francisco, California, November 13 to 16, 1989. t Reprint requests: Deborah A. Metzger, M.D., Ph.D., Department of Reproductive Endocrinology, University of Connecticut Health Center, Farmington, Connecticut 06030.
252
Chaff'kin et al.
Although the efficacy of the combined treatment has been demonstrated to be superior to hMG or lUI alone in unexplained infertility,3 the relative efficacy of hMG, lUI, and hMGjlUI has not been adequately defined for other causes of infertility. A comparison of the cycle fecundity rate for hMGj lUI versus that associated with the use of hMG or lUI alone would provide the basis for assessment of whether the relative chances of pregnancy justify the increased cost and may help us define the best treatment for each of the various infertility diagnoses. Thus, we performed this retrospective study to evaluate the hypothesis that the cycle fecundity rate is improved with controlled hMG superovulation combined with lUI. In addition, we
Combined hMGjIUI versus hMG or lUI alone
Fertility and Sterility
also evaluated the efficacy of superovulation in conjunction with lUI in patients who had previously failed either hMG or lUI alone. MATERIALS AND METHODS
The records of 322 patients who had been treated with lUI, controlled hMG superovulation, or hMG combined with lUI (hMG/IUI) during 1986 to 1989 at the University of Connecticut Health Center were reviewed retrospectively. Before treatment, all couples underwent a complete infertility evaluation that included ovulation assessment by basal body temperature (BBT) recording and endometrial biopsy, postcoital test (PCT), hysterosalpingogram (HSG), semen analysis, and, in the majority of cases, diagnostic laparoscopy. We excluded couples in whom anovulation was the sole documented cause of infertility. Patients were grouped according to infertility diagnosis. When multiple factors were present, each factor was separately tabulated. Infertility subgroups were defined as follows: (1) male factor in which two or more semen analyses obtained at least 1 month apart revealed a sperm density < 20 X 106 sperm/mL and/or
20
E
0
Do
-• c c
~ A
0
• -; ::I
0
1
0
100
2
5
4
3
0
8
0
2
3
4
Cycle number
HMG
Figure 3 Cumulative PRs with combined hMG/IUI therapy in patients who previously failed either lUI or hMG therapy.
80
C
o t:o
80
!! A
40
was similar to that of patients who received hMG in combination with lUI from the onset (Fig. 3).
I
20
DISCUSSION
A
i::a
E
0
::a
0
U
100
2
1
3
4
3
4
5
8
HMG/IUI
80 80
40 20
2
5
6
Cycle Figure 2 Cumulative PRs by therapeutic groups (lUI, hMG, or hMG/IUI) with each infertility factor examined separately.
(cycle fecundity 14%). The cumulative PR after the initiation of hMGjIUI therapy in these treatment failure groups (58% after 4 cycles oftherapy) Table 2
Cycle Fecundity Rates by Cycle Number"
Cycle number
lUI
HMG
HMG/1U1
1 2 3 4
4.5 5.8 0.0 4.0 5.8
4.3 7.1 7.5 9.5 7.6
19.0 18.5 25.5 9.4 2.8
5 " Values are percents.
Vol. 55, No.2, February 1991
Intrauterine insemination has been employed for many years in the treatment of the infertile couple. Success rates with male factor and unexplained infertility have generally been discouraging,3,5-14 although patients with cervical factor infertility appear to fare somewhat betterp-21 A literature review by Allen et al. 19 noted an overall PR of 25% for lUI-treated male factor infertility (range 7%12 to 66%13) and 60% for cervical factor infertility (range 52%16 to 70%13). The mean overall PR reported was 28% (range 3.4%20 to 62.0%13), similar to our results in the lUI alone group. Although hMG has been recently advocated21 for the treatment of ovulatory women with longstanding idiopathic infertility, improvement in cycle fecundity in ovulatory women with male factor infertility, cervical factor infertility, or endometriosis has not been demonstrated when hMG is used alone. Our results suggest that hMG alone is of minimal therapeutic benefit when compared with the cycle fecundity and cumulative PRs associated with combined hMGjIUI therapy. Considering the expense and risks involved with controlled hMG superovulation therapy, it is logical to maximize the benefits to the patient by the addition of lUI. The results of our experience with hMG combined with lUI are very encouraging and similar to those reported by other investigators, although a direct comparison of cycle fecundity with hMG, lUI, and hMGjIUI has not been previously reported. Recently, Dodson and colleagues1 reported a cycle fecundity with hMG JIUI therapy of 29% for
Chaffkin et al.
Combined hMG/IUI versus hMG or lUI alone
255
cervical factor, 17% for endometriosis, and 19% for idiopathic infertility. Couples with abnormalities in semen analysis were excluded from this study. Serhal et a1. 3 reported a cycle fecundity rate of 26.4% with hMG/IUI in the treatment of unexplained infertility and noted this to represent a 10fold increase when compared with patients who received lUI alone. Corson et a1. 2 reported a statistically significant increase in cycle fecundity rate (from 5% to 11%) with hMG/IUI treatment as compared with lUI alone in patients who had cervical factor abnormalities. Our results confirm the therapeutic efficacy of the combined hMG/IUI therapy as reported in these studies and suggest that the combined therapy is much more effective than either lUI or hMG alone for all infertility factors studied. Attempts at improving PRs with infertility associated with endometriosis have been somewhat discouraging. Recent controlled studies demonstrate no enhancement of fertility after medical therapy with both treated and expectantly managed groups having cycle fecundity rates between 2% and 6%.22 Although women with mild and moderate endometriosis fare as well with in vitro fertilization (IVF) as women with tubal factor infertility,20 there are no less invasive procedures with demonstrated efficacy in enhancing fertility in endometriosis. The results of this study are significant for two reasons: (1) all of the women in the study had undergone laparoscopic laser surgery as initial treatment for their endometriosis and failed to conceive 6 to 24 months after treatment. Thus, these patients represent a group of treatment failures, and (2) the cycle fecundity rates observed with combined hMG/IUI are two to six times higher than reported with expectant management or hormonal therapy and two times that observed with hMG alone. Thus, these results suggest that combined hMG/ lUI therapy may be an effective alternative to IVF for the treatment of infertility associated with endometriosis. Several factors can account for the dramatic improvement in cycle fecundity with hMG/IUI therapy, regardless of the apparent etiology of infertility. The number and concentration of sperm in the upper genital tract are increased, while simultaneously, a greater number of target oocytes are made available. This may improve chances of fertilization where a gametotoxic effect may be present, as has been suggested for endometriosis-associated infertility.24 Occult ovulatory disturbances may be corrected and barriers to sperm that may 256
Chaffkin et al.
be present in the cervical mucus are bypassed. The procedure also offers the technical benefit of improving the timing of insemination relative to ovulation. The advantages of hMG/IUI are similar in theory to those offered by gamete intrafallopian transfer (GIFT). Both techniques increase the number of male and female gametes present at the site of fertilization. The cycle fecundity rate in our experience is equivalent to that reported for IVF but not quite as good as GIFT.25 However, hMG/IUI therapy avoids the need for general anesthesia, invasive oocyte retrieval, and provides a significant savings in cost. Intensive monitoring, however, is still required to minimize the risks of ovarian hyperstimulation and multiple pregnancy, which must be considered when evaluating this mode of therapy. In conclusion, we found the cycle fecundity rates and cumulative PRs to be significantly greater using a combination ofhMG and lUI when compared with either modality used alone in the treatment of male factor, cervical factor, or unexplained infertility. The increase in cycle fecundity rate in patients with laparoscopic evidence of endometriosis approached, but did not meet, the criteria for statistical significance when comparing hMG/IUI therapy with hMG alone. Human menopausal gonadotropin/lUI appears to be a viable treatment option in patients with infertility refractory to other treatments, or before the institution of IVF/GIFT therapy in patients with patent fallopian tubes.
REFERENCES 1. Dodson WC, Whitesides DB, Hughes CL, Jr, Easley HA
2.
3.
4.
5.
6.
Combined hMGjIUI versus hMG or lUI alone
III, Haney AF: Superovulation with intrauterine insemination in the treatment of infertility: a possible alternative to gamete intrafallopian transfer and in vitro fertilization. Fertil SteriI48:441, 1987 Corson SL, Batzer FR, Gocial B, Maislin G: Intrauterine insemination and ovulation stimulation as treatment of infertility. J Reprod Med 34:397,1989 Serhal PF, Katz M, Little V, Woronowski H: Unexplained infertility-the value Pergonal superovulation combined with intrauterine insemination. Fertil Steril49:602, 1988 Cramer DW, Walker AM, Schiff I: Statistical methods in evaluating the outcome of infertility therapy. Fertil Steril 32:80,1979 Kerin JFP, Peek J, Warnes GM, Kirby C, Jeffrey R, Matthews CD, Cox LW: Improved conception rate after intrauterine insemination of washed spermatozoa from men with poor quality semen. Lancet 1:553, 1984 Hoing L, Devroey P, Van Steirteghem A: Treatment of infertility because of oligoasthenoteratospermia by transcervical intrauterine insemination of motile spermatozoa. Fertil Steril 45:388, 1986
Fertility and Sterility
7. Toffie RC, Nagel TC, Tagatz GE, Phansey SA, Okagaki T, Wavrin CA: Intrauterine insemination: the University of Minnesota experience. Fertil Steril43:743, 1985 8. Hewitt J, Cohen J, Krishnaswamy V, Fehilly CB, Steptoe PC, Walters DE: Treatment of idiopathic infertility, cervical mucus hostility, and male infertility: artificial insemination with husband's semen or in vitro fertilization? Fertil Steril44:350, 1985 9. DiMarzo SJ, Rakofl' JS: Intrauterine insemination with husband's washed sperm. Fertil Steril46:470, 1986 10. Makler A: Washed intrauterine insemination in the treatment of idiopathic infertility. Semin Reprod Endocrinol5: 35, 1987 11. Sher G, Knutzen VK, Stratton CJ, Montakhab MM, Allenson SG: In vitro sperm capacitation and transcervical intrauterine insemination for the treatment of refractory infertility: phase 1. Fertil Steril41:260, 1984 12. Wiltbank MC, Kosasa TS, Rogers BJ: Treatment of infertile patients by intrauterine insemination of washed spermatozoa. Andrologia 17:22, 1985 13. Barwin BN: Intrauterine insemination of husband's semen. J Reprod Fertil36:101, 1974 14. Yovich JL, Matson PL: The treatment of infertility by the high intrauterine insemination of husband's washed spermatozoa. Hum Reprod 3:939, 1988 15. Lalich R, Marut E, Prins G, Scommegna A: Life table analysis of intrauterine insemination pregnancy rates. Am J Obstet GynecoI158:980, 1988 16. Glezerman M, Bernstein D, Insler V: The cervical factor of infertility and intrauterine insemination. Int J Fertil29:16, 1984
Vol. 55, No.2, February 1991
17. Confino E, Friberg J, Dudkiewicz AB, Gleicher N: Intrauterine insemination with washed human spermatozoa. Fertil Steril 46:55, 1986 18. Quagliarello J, Arny M: Intracervical versus intrauterine insemination: correlation of outcome with antecedent postcoital testing. Fertil Steril 46:870, 1986 19. Allen NC, Herbert CM, Maxson WS, Rogers BJ, Diamond MP, Wentz AC: Intrauterine insemination: a critical review. Fertil Steril 44:569, 1985 20. Mastroianni L, Jr, Laberge JL, Rock J: Appraisal of the efficacy of artificial insemination with husband's sperm and evaluation of insemination technics. Fertil Steril 8:260, 1957 21. WeIner S, DeCherney AH, Lake Polan M: Human menopausal gonadotropins: a justifiable therapy in ovulatory women with long-standing idiopathic infertility. Am J Obstet GynecoI158:111, 1988 22. Olive DL, Haney AF: Endometriosis-associated infertility: a critical review of therapeutic approaches. Obstet Gynecol Survey 41:538,1986 23. Matson PL, Yovich JL: The treatment of infertility associated with endometriosis by in vitro fertilization. Fertil SteriI46:432, 1986 24. Syrop CH, Halme J: Peritoneal fluid environment and infertility. Fertil Steril48:1, 1987 25. Medical Research International and the Society for Assisted Reproductive Technology, The American Fertility Society: In vitro fertilization-embryo transfer in the United States: 1988 results from the IVF-ET Registry. Fertil Steril 53:13,1990
Chaffkin et al.
Combined hMG/IUI versus hMG or lUI alone
257
