Comparison of fallopian tube sperm perfusion and intrauterine tuboperitoneal insemination: a prospective randomized study

Transcription

1 Comparison of fallopian tube sperm perfusion and intrauterine tuboperitoneal insemination: a prospective randomized study Leonidas Mamas, M.D., Ph.D. Neogenesis IVF Center, Athens, Greece Objective: To evaluate the results of two different methods of insemination: fallopian tube sperm perfusion (FSP) with 4 ml of inseminate and intrauterine tuboperitoneal insemination (IUTPI) with 10 ml of inseminate. Design: Prospective randomized clinical study. Setting: Private infertility center. Patient(s): Two hundred seventy-six couples, undergoing 403 cycles, with unexplained infertility, mild or moderate male infertility, or mild or moderate endometriosis. Intervention(s): Patients were assigned randomly to either FSP (group A, n 138) or IUTPI (group B, n 138) treatment. Both groups followed the same mild ovarian stimulation protocol. Main Outcome Measure(s): Ninety-five overall pregnancies: 35 in group A (FSP) and 60 in group B (IUTPI). Result(s): The pregnancy rate per cycle (presence of gestational sac with heart beats) was 17.6% in group A (n 199) and 29.4% in group B (n 204). These differences were statistically significant (P.007). The odds ratio of getting pregnant, per patient, in group B was 2.26 (95% confidence interval ) compared with group A. Conclusion(s): The results of this study indicate that IUTPI may prove to be a useful technique in the treatment of unexplained infertility, mild or moderate male infertility, and mild or moderate endometriosis. Three attempts of IUTPI may be beneficial before moving on to more invasive and expensive methods of assisted reproduction techniques. (Fertil Steril 2006;85: by American Society for Reproductive Medicine.) Key Words: Fallopian tube sperm perfusion, intrautero tuboperitoneal insemination, intrauterine insemination, infertility Received April 6, 2005; revised and accepted August 9, Reprint requests: Leonidas Mamas, M.D., Neogenesis IVF Center, 3 Kifisias Ave, Marousi, Athens, Greece (FAX: ; leonidasmamas@neogenesis.gr). The method of fallopian tube sperm perfusion (FSP) was first described in 1992, by Kahn et al. (1). This method involved the use of 4 ml of inseminate, a considerably higher volume than the 0.5 ml previously used for intrauterine insemination (IUI). Leakage of the inseminate was avoided by clamping the cervix and the pressure built up in the uterine cavity led to uterotubal flushing. Consequently, the number of motile spermatozoa was increased in the female genital tract, thus overcoming low sperm count, suboptimal spermatozoa, or total absence of spermatozoa at the site of fertilization. The results were encouraging and were confirmed in two more publications (2, 3). It was observed that the number of spermatozoa distributed within the fallopian tubes around ovulation after IUI was low. Only a median of 251 spermatozoa were recovered by flushing the tubes (4), and there was only a 49% chance of peritoneal spermatozoa to be found, even when all semen characteristics were normal (5). Ripps et al. (6) showed that although the number of peritoneal spermatozoa recovered at laparoscopy after IUI was very low, their number increased after uterotubal flushes. In addition, uterotubal flushes required a certain pressure for the achievement of intrauterine perfusion and spill in normal tubes or in tubes with minimal adhesions (7), because in the midfollicular phase and before ovulation the endometrial glandular lumens of the fallopian tubes were narrowed and contained quantities of granular and membranous material, as well as increasing amounts of cytoplasmic debris, cellular fragments (8), and tubal ostium membranes (9). In 1993, Li (10) described another technique for FSP with good results, by using a Foley size 8 pediatric catheter with the balloon inflated in the uterine cavity to seal the uterocervical junction. Fanchin et al. (11) proposed the Fallopian Sperm Transfer (FAST) system for FSP, with pregnancy results twice as high as standard IUI. The author of the current article presented the use of a speculum specially designed for FSP, the double nut bivalve (DNB) speculum with modified tips which firmly clamp the cervix and the cervical canal, preventing any leakage of the inseminate and leading to a higher fallopian sperm perfusion with results twice as promising as standard IUI (12). Observations in our clinical practice showed that occasionally the 4 ml of inseminate used for FSP was not sufficient to overcome the tubal ostia, because the intrauterine pressure caused by this volume was not adequate. Therefore, a larger volume of inseminate was gradually used, ultimately reaching 10 ml, while simultaneously checking the intrauterine pressure. There was an unexpected increase /06/$32.00 Fertility and Sterility Vol. 85, No. 3, March 2006 doi: /j.fertnstert Copyright 2006 American Society for Reproductive Medicine, Published by Elsevier Inc. 735

2 of pregnancy rates when a larger volume of inseminate was used. Besides, 10 ml of contrast medium is also used in hysterosalpingography (HSG) (13). In addition, the possible therapeutic effect of HSG has been extensively discussed in various articles over the last decades, because the rate of live births increases after HSG, especially in patients with unexplained infertility, supporting the hypothesis that tubal plugs may be involved in proximal tubal blockage (14, 15). The volume of 10 ml of inseminate was sufficient to fill the uterine cavity, pass through the interstitial part of the tubes and the ampulla, and finally reach the peritoneal cavity and the pouch of Douglas where it would be mixed with the peritoneal and follicular fluids. In this way intrauterine tuboperitoneal insemination (IUTPI) was achieved. This prospective randomized study was designed to compare the results of FSP and IUTPI. MATERIALS AND METHODS Patient Selection During the 30-month period from July 1, 2002, to December 31, 2004, 276 couples undergoing 403 cycles were treated in our IVF center. Couples were asked whether they would like to participate in this study. All couples suffered from unexplained infertility, mild or moderate male infertility, or mild or moderate endometriosis after treatment (16). All women had a regular menstrual cycle of days. Spontaneous ovulation was checked by vaginal ultrasound and normal serum progesterone concentrations ( 10 ng/ml) in midluteal phase serum. Serum levels of FSH of 10 U/L on day 3 indicated adequate ovarian reserve, whereas LH, PRL, T, sex hormone binding globulin, and thyroid hormone concentrations had to be in the normal range. Chlamydia detection tests also were performed. The body mass index had to be between 20 and 29 kg/m 2. Men were asked to have a semen analysis and, in cases of infertility, the test was repeated. Semen analysis was evaluated according to the World Health Organization criteria (17), sperm morphology was assessed using strict criteria (18), and the inseminate motile sperm count (IMC) recovered after gradients had to be more than Two hundred thirty-one patients had primary and 45 secondary infertility. The mean duration of infertility was years (range 1 6 years) for group A (FSP) and years (range 2 6years ) for group B (IUTPI). All patients had undergone HSG in the last 12 months that showed normal uterine cavity and bilateral tubal patency (19, 20). Thirty-six of them had undergone laparoscopy because of suspected tubal disease. Patients had to be younger than 40 years of age. Controlled Ovarian Stimulation All patients underwent the same controlled ovarian stimulation protocol. The protocol consisted of clomiphene citrate followed by highly purified urinary FSH (hpufsh) (Altermon; IBSA, Lamone, Switzerland) or recombinant FSH (recfsh) (Puregon; Organon, Oss, The Netherlands; or Gonal-f; Serono, Geneva, Switzerland). From day 2 to day 6 of the cycle, 100 mg clomiphene citrate was administered daily. For patients with body mass index between 20 and 24 kg/m 2, clomiphene was followed by either 75 IU hpufsh, in 264 cycles, or 75 IU recfsh, in 60 cycles, from day 6 to day 9. For patients with body mass index between 25 and 29 kg/m 2, clomiphene was followed by 150 IU of either hpufsh, in 64 cycles, or 150 IU recfsh, in 15 cycles, from day 6 9. A transvaginal ultrasonography was performed on day 2 of the cycle (check scan), which was repeated on the tenth day for the assessment of the number and diameter of the follicles, as well as the thickness and the morphology of the endometrium. The serum E 2 was also measured on that day. The administration of hpufsh or recfsh was continued to the tenth day or, in some cases, to the eleventh or twelfth day. When the leading follicle was mm in diameter and 2 3 follicles of mm were also present, 5,000 IU hcg (Pregnyl; Organon) was administered. In addition, the transvaginal power Doppler utrasonography should show highgrade perifollicular vascularity (21). The treatment cycles were cancelled when serum E 2 concentration exceeded 1,000 pg/ml or more and four follicles or more had matured, because of the risk of multiple gestation (22 24). Insemination was performed h after hcg administration. Randomization Women were allocated randomly to group A (FSP), or group B (IUTPI) on the day of hcg administration with sealed envelopes and remained in the same group throughout all attempts. Sperm Preparation Semen was collected by masturbation into a sterile jar following 3 4 days of sexual abstinence. Semen analysis was evaluated after liquefaction according to the World Health Organization criteria (17), whereas sperm morphology was assessed using strict criteria (18). A two-layer gradient technique was used for sperm preparation. One milliliter of 45% SpermGrad (Vitrolife, Kungsbacka, Sweden) Ham s F-10 (Gibgo BRL; Life Technologies, Paisley, Scotland) was layered over 1 ml of 90% SpermGrad, in a 15-mL conical centrifuge tube. The undiluted semen was layered over this gradient and the tube was centrifuged for 20 minutes at 250g. The supernatant was discarded and the pellet diluted in 7 ml Universal IVF medium (MediCult, Copenhagen, Denmark) and recentrifuged for 8 min at 500g. The supernatant was discarded after recentrifugation and the remaining final pellet was diluted in 4 ml or 10 ml of Universal IVF medium for FSP and IUTPI, respectively. All solutions were also analyzed to evaluate the IMC. 736 Mamas FSP or IUTPI? Vol. 85, No. 3, March 2006

3 Insemination Insemination was performed h after hcg administration in both groups. Fallopian tube sperm perfusion with 4 ml of inseminate was carried out using the DNB Speculum (Parthenon Medical, Athens, Greece), which was specially designed for clamping and sealing the cervix. The cervix and vaginal fornices were cleaned with a cotton swab and the external cervical os with antiseptic. The use of the DNB Speculum has been described elsewhere (12). Fallopian tube sperm perfusion was performed slowly, 4 ml/min, using an 18-mm insemination catheter (Wallace-Smiths, Hythe, Kent, UK) which was atraumatically inserted through the cervical canal into the upper part of the uterine cavity. No leakage was usually observed. The speculum was kept locked, clamping the cervix for at least one or two minutes. Before removing the DNB Speculum, the DNB test was performed by pulling the piston of the syringe in order to check the amount of the inseminate remaining in the uterine cavity. If it was more than 1 ml, insemination was repeated. The DNB speculum was removed only when the inseminate retrieved was less than 1 ml. Intrauterine tuboperitoneal insemination with 10 ml of inseminate was also carried out using the DNB Speculum cervical clamp. Insemination was performed slowly, in 1 2 min while simultaneously checking the intrauterine pressure with a Schulze manometer (Schulze, Tuttlingen, Germany) used in HSG. The lowest pressure checked was 80 mm Hg, the highest 240 mm/hg, and the mean 140 mm Hg. The pressure gradually built up in the uterine cavity allowed the inseminate to overcome the tubal ostia and, by flushing the fallopian tubes, reach the pouch of Douglas. Intraperitoneal insemination was thus achieved. The speculum was kept locked, clamping the cervix for at least one more minute. The DNB test was performed as described above. One insemination was performed per cycle, and no infection was observed. Luteal Support The luteal phase was supported by oral supplementation of 300 mg micronized progesterone (Utrogestan; Laboratoires Besins Incovesco, Paris, France). Statistical Analysis The primary aim of this study was to compare the overall pregnancy rate per group. Based on interim results and existing data, we assumed that FSP treatment would yield a pregnancy rate of 20%. Sample size calculation showed that a 15% increase of the overall pregnancy rate could be detected between the two groups with a power of 80% using a 2 test. Pregnancy rates per cycle were also calculated and compared by a 2 test at.05. Baseline characteristics of women in the two groups were presented and their mean values were compared by independentsamples t test at.05. Clinical pregnancy was defined by the presence of fetal heart beat detected by ultrasound examination. RESULTS Of the 276 couples enrolled in this study, 138 were randomly allocated to group A (FSP) and 138 in group B (IUTPI). All patients underwent a total of 403 treatment cycles: group A (n 199): FSP with 4 ml of sperm inseminated; group B (n 204): IUTPI with 10 ml of sperm inseminated. As far as the baseline characteristics of the patients of both groups are concerned, there was no statistical difference in the age, the number of mature follicles ( 17 mm diameter), serum E 2 levels, the thickness of endometrium as measured by vaginal ultrasound on the day of randomization (day of hcg administration), and the IMC, obtained after preparation (Table 1). In both treatment groups, 95 women got pregnant, yielding an overall pregnancy rate of 34.4%. Considering the total number of achieved pregnancies, we observed that 35/138 (25.4%) pregnancies had been achieved in group A, and TABLE 1 Baseline characteristics of the study groups. Group A (FSP) Group B (IUTPI) P Age Follicles E Endometrium thickness IMC Note: FSP fallopian tube sperm perfusion; IUTPI intrauterine tuboperitoneal insemination; IMC inseminate motile sperm count. Mamas. FSP or IUTPI? Fertil Steril Fertility and Sterility 737

4 TABLE 2 Number of pregnancies and corresponding rate per cycle in the two groups. Treatment cycle Group A (FSP) Group B (IUTPI) No. cycles No. pregnancies Rate (%) No. cycles No. pregnancies Rate (%) P First Second Third Total Mamas. FSP or IUTPI? Fertil Steril /138 (43.5%) in group B (P.002). The odds ratio of getting pregnant in group B compared with group A is 2.26 (95% confidence interval ). The total rate of pregnancies per cycle in group A was 17.6% and in group B 29.4% (P.007) (Table 2). Detailed information about the pregnancy rates in each cycle for the two groups is presented in Table 2. The difference of pregnancy rates in the first cycle was statistically significant (P.012), whereas in the second and third cycles differences were not statistically significant (P.236; P.693; respectively), although the IUTPI method still yielded higher pregnancy rates. The above results are illustrated in Figure 1. Four missed abortions occurred in group A (FSP) and five in group B (IUTPI). Three twin pregnancies occurred in group A (FSP) and five in group B (IUTPI), as well as a set of quadruplets, which was reduced to twin pregnancy. Three cases of mild ovarian hyperstimulation syndrome (OHSS) occurred in both groups. No case of moderate or severe OHSS was observed (25). FIGURE 1 Pregnancy rates for FSP and IUTPI treatments in each cycle. Mamas. FSP or IUTPI? Fertil Steril DISCUSSION Interest in IUI as well as FSP and other similar techniques was renewed by specialists when new sperm preparation methods were developed for IVF. These procedures improve the fertilizing ability of the sperm in vivo and in vitro by removing most adverse agents such as seminal plasma, prostaglandins, bacteria, white blood cells, cellular debris, immature germ cells, and dead, damaged, and abnormal spermatozoa which produce free oxygen radicals (26 28). The current prospective randomized study presents the encouraging results of IUTPI (inseminate volume 10 ml) compared with FSP (4 ml inseminate) in cases with unexplained infertility, mild or moderate male factor infertility, or mild or moderate endometriosis. The pregnancy rates per cycle were 17.6% for the FSP group and 29.4% for the IUTPI group. Both groups followed the same mild ovarian stimulation protocol, which was cost-effective and well tolerated and required fewer injections per cycle (29). There was no statistically significant difference regarding the age of the patients treated, the mean number of follicles, serum E 2, endometrial thickness on the day of hcg administration, and the IMC. All cases had one insemination per cycle (30, 31). Fallopian tube sperm perfusion with controlled ovarian stimulation was first described by Khan et al. in 1992, showing encouraging results for cases of unexplained infertility, with pregnancy rates ranging from 24.1% to 40.0% (1 3, 10 12). Although there are a few studies that report that FSP produces no statistically significant results compared to standard IUI in cases of unexplained infertility (32 36), two meta-analyses performed in 1999 (37) and 2004 (38) showed that FSP is beneficial in cases of unexplained infertility after ovarian stimulation. Ricci et al., 2001(39), confirms the good results of FSP for unexplained infertility, whereas Strandell et al., 2003 (40), showed that pregnancy results after FSP were not impaired by lower sperm count and morphology. The wide range of the results given by FSP enthusiasts may be due to the different instruments used in order to facilitate the method (Alis clamp, Foley catheter, FAST system, DNB Speculum, ZUI catheter, HSG device). 738 Mamas FSP or IUTPI? Vol. 85, No. 3, March 2006

5 In this study, the DNB Speculum was used. The intrauterine pressure was checked with a manometer and ranged from 80 to 240 mm Hg with mean reading of 140 mm Hg. Baker and Adamson (7) reported lower readings probably because the intrauterine pressure was measured in the midfollicular phase, whereas in the current study intrauterine pressure was checked around ovulation, when the endometrial glandular lumen of the interstitial part of the fallopian tube is narrowed and contains quantities of granular and membranous material, as well as amounts of cytoplasmic debris and cellular fragments (8). The highest pressure was observed when 3 4 ml of sperm was inseminated which caused the tubal ostia to open. As soon as the inseminate passed through the tubal ostia and into the fallopian tubes, the pressure, according to the manometer, dropped to mm Hg. In addition, the opening of the tubal ostia could also be detected by the decrease of the syringe piston s resistance. The volume of 10 ml of inseminate used in IUTPI was sufficient to fill the uterine cavity and, through the fallopian tubes, reach the peritoneal cavity and the pouch of Douglas where it would be mixed with the peritoneal and follicular fluids, thus accomplishing a noninvasive intraperitoneal insemination by flushing the tubes. Guidi et al. (41) showed that peritoneal fluids from hormonally stimulated cycles sustained better sperm motility than spontaneous cycles. Revelli et al. (42) showed that follicular fluid in hormonally stimulated cycles influences progressive motility of the sperm positively while sustaining the number of motile spermatozoa. These studies support the good results of intraperitoneal insemination (IPI) in humans with very low sperm count (43 46), which become even better when IPI is combined with IUI (47). Intraperitoneal insemination is also successfully performed in mammals (48). However, because IPI is an invasive technique, it should be chosen when other methods are difficult to perform, as, for example, in the presence of a tight cervical canal (49, 50). The excellent results of IUTPI (29.4%) may be attributed to the efficient flushing of the fallopian tubes obtained by the 10 ml of inseminate, thus performing a noninvasive IPI. In conclusion, IUTPI may prove a useful technique in the treatment of unexplained infertility, mild or moderate male infertility, and mild or moderate endometriosis. Three attempts of IUTPI may be beneficial before moving on to more invasive and expensive methods of assisted reproduction techniques. REFERENCES 1. Kahn JA, von During V, Sunde A, Sordal T, Molne K. Fallopian tube sperm perfusion. First clinical experience. Hum Reprod 1992;7: Kahn JA, Sunde A, Koskemies A, von During V, Sordal T, Christensen F, et al. Fallopian tube sperm perfusion (FSP) versus intra-uterine insemination (IUI) in the treatment of unexplained infertility: a prospective randomized study. Hum Reprod 1993;8: Kahn JA, Sunde A, von During V, Sordal T, Molne K. Treatment of unexplained infertility. Fallopian tube sperm perfusion (FSP). Acta Obstet Gynecol Scand 1993;72: Williams M, Hill CJ, Scudamore I, Dunphy B, Cooke ID, Barratt CL. Sperm numbers and distribution within the human fallopian tube around ovulation. Hum Reprod 1993;8: Mortimer D, Templeton AA. Sperm transport in the human female reproductive tract in relation to semen analysis characteristics and time of ovulation. J Reprod Fertil 1982;64: Ripps BA, Minhas BS, Carson SA, Buster JE. Intrauterine insemination in fertile women delivers larger numbers of sperm to the peritoneal fluid than intracervical insemination. Fertil Steril 1994;61: Baker VL, Adamson GD. Threshold intrauterine perfusion pressures for intraperitoneal spill during hydrotubation and correlation with tubal adhesive disease. Fertil Steril 1995;64: Amso NN, Crow J, Lewin J, Shaw RW. A comparative morphological and ultrastructural study of endometrial gland and fallopian tube epithelia at different stages of the menstrual cycle and the menopause. Hum Reprod 1994;9: Coeman D, Belle YV, Vanderick G. Tubal ostium membranes and their relation to infertility. Fertil Steril 1995;63: Li TC. A simple, noninvasive method of fallopian tube sperm perfusion. Hum Reprod 1993;8: Fanchin R, Olivennes F, Righini C, Hazout A, Schwab B, Frydman R. A new system for fallopian tube sperm perfusion leads to pregnancy rates twice as high as standard intrauterine insemination. Fertil Steril 1995;64: Mamas L. Higher pregnancy rates with a simple method for fallopian tube sperm perfusion, using the cervical clamp double nut bivalve speculum in the treatment of unexplained infertility: a prospective randomized study. Hum Reprod 1996;11: Shalev J, Krissi H, Blankstein J, Meizner I, Ben-Rafael Z, Dicker D. Modified hysterosalpingography during infertility work-up: use of contrast medium and saline to investigate mechanical factors. Fertil Steril 2000;74: Spring DB, Barkan HE, Pruyn SC. Potential therapeutic effects of contrast materials in hysterosalpingography: a prospective randomized clinical trial. Kaiser Permanente Infertility Work Group. Radiology 2000;214: Johnson N, Vandekerckhove P, Watson A, Lilford R, Harada T, Hughes E. Tubal flushing for subfertility. Cochrane Database Syst Rev 2002; 3:CD American Society for Reproductive Medicine. Revised American Society for Reproductive Medicine classification of endometriosis: Fertil Steril 1997;67: World Health Organization. WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction. 4th ed. Cambridge (UK): Press Syndicate of the University of Cambridge; Van Waart J, Kruger TF, Lombard CJ, Ombelet W. Predictive value of normal sperm morphology in intrauterine insemination (IUI): a structured literature review. Hum Reprod Update 2001;7: Fatum M, Laufer N, Simon A. Investigation of the infertile couple: should diagnostic laparoscopy be performed after normal hysterosalpingography in treating infertility suspected to be of unknown origin? Hum Reprod 2002;17: Tanahatoe SJ, Hompes PG, Lambalk CB. Investigation of the infertile couple: should diagnostic laparoscopy be performed in the infertility work up programme in patients undergoing intrauterine insemination? Hum Reprod 2003;18: Bhal PS, Pugh ND, Gregory L, O Brien S, Shaw RW. Perifollicular vascularity as a potential variable affecting outcome in stimulated intrauterine insemination treatment cycles: a study using transvaginal power Doppler. Hum Reprod 2001;16: Dickey RP, Taylor SN, Sartor BM, Rye PH, Pyrzak R. Relationship of follicle numbers and estradiol levels to multiple implantation in 3,608 intrauterine insemination cycles. Fertil Steril 2001;75: Tur R, Barri PN, Coroleu B, Buxaderas R, Martinez F, Balasch J. Risk factors for high-order multiple implantation after ovarian stimulation Fertility and Sterility 739

6 with gonadotrophins: evidence from a large series of 1878 consecutive pregnancies in a single centre. Hum Reprod 2001;16: Healy D, Rombauts L, Vollenhoven B, Kovacs G, Burmeister L. One triplet pregnancy in 510 controlled ovarian hyperstimulation and intrauterine insemination cycles. Fertil Steril 2003;79: Schenker JG. Prevention and treatment of ovarian hyperstimulation. Hum Reprod 1993;8: Van der Ven H, Bhattacharyya AK, Binor Z, Leto S, Zaneveld LJ. Inhibition of human sperm capacitation by a high-molecular-weight factor from human seminal plasma. Fertil Steril 1982;38: Aitken RJ, Clarkson JS. Cellular basis and its association with the genesis of reactive oxygen species by human spermatozoa. J Reprod Fertil 1987;81: Henkel RR, Schill WB. Sperm preparation for ART. Reprod Biol Endocrinol 2003;1: Nuojua-Huttunen S, Tomas C, Bloigu R, Tuomivaara L, Martikainen H. Intrauterine insemination treatment in subfertility: an analysis of factors affecting outcome. Hum Reprod 1999;14: Alborzi S, Motazedian S, Parsanezhad ME, Jannati S. Comparison of the effectiveness of single intrauterine insemination (IUI) versus double IUI per cycle in infertile patients. Fertil Steril 2003;80: Cantineau AE, Heineman MJ, Cohlen BJ. Single versus double intrauterine insemination in stimulated cycles for subfertile couples: a systematic review based on a Cochrane review. Hum Reprod 2003;18: Gregoriou O, Pyrgiotis E, Konidaris S, Papadias C, Zourlas PA. Fallopian tube sperm perfusion has no advantage over intra-uterine insemination when used in combination with ovarian stimulation for treatment of unexplained infertility. Gynecol Obstet Invest 1995;39: Nuojua-Huttunen S, Tuomivaara L, Juntunen K, Tomas C, Martikainen H. Comparison of fallopian tube sperm perfusion with intrauterine insemination in the treatment of infertility. Fertil Steril 1997;67: El Sadek MM, Amer MK, Abdel-Malak G. Questioning the efficacy of fallopian tube sperm perfusion. Hum Reprod 1998;13: Ng EH, Makkar G, Yeung WS, Ho PC. A randomized comparison of three insemination methods in an artificial insemination program using husbands semen. J Reprod Med 2003;48: Biacchiardi CP, Revelli A, Gennarelli G, Rustichelli S, Moffa F, Massobrio M. Fallopian tube sperm perfusion versus intrauterine insemination in unexplained infertility: a randomized, prospective, crossover trial. Fertil Steril 2004;81: Trout SW, Kemmann E. Fallopian sperm perfusion versus intrauterine insemination: a randomized controlled trial and metaanalysis of the literature. Fertil Steril 1999;71: Cantineau AE, Heineman MJ, Al-Inany H, Cohlen BJ. Intrauterine insemination versus fallopian tube sperm perfusion in nontubal subfertility: a systematic review based on a Cochrane review. Hum Reprod 2004;19: Ricci G, Nucera G, Pozzobon C, Boscolo R, Giolo E, Guaschino S. A simple method for fallopian tube sperm perfusion using a blocking device in the treatment of unexplained infertility. Fertil Steril 2001;76: Strandell A, Bergh C, Soderlund B, Lundin K, Nilsson L. Fallopian tube sperm perfusion: the impact of sperm count and morphology on pregnancy rates. Acta Obstet Gynecol Scand 2003;82: Guidi F, Revelli A, Soldati G, Stamm J, Massobrio M, Piffaretti-Yanez A, et al. Influence of peritoneal fluid from spontaneous and stimulated cycles on sperm motility in vitro. Andrologia 1993;25: Revelli A, Soldati G, Stamm J, Massobrio M, Topfer-Petersen E, Balerna M. Effect of volumetric mixtures of peritoneal and follicular fluid from the same woman on sperm motility and acrosomal reactivity in vitro. Fertil Steril 1992;57: Seracchioli R, Melega C, Maccolini A, Cattoli M, Bulletti C, Bovicelli L, et al. Pregnancy after direct intraperitoneal insemination. Hum Reprod 1991;6: Crosignani PG, Ragni G, Finzi GC, De Lauretis L, Olivares MD, Perotti L. Intraperitoneal insemination in the treatment of male and unexplained infertility. Fertil Steril 1991;55: Ragni G, Parazzini F, Sapienza F, Chatenoud L, De Lauretis L, Perotti L, et al. Semen parameters and conception rates after intraperitoneal insemination. Gynecol Obstet Invest 1997;44: Turhan NO, Artini PG, D Ambrogio G, Droghini F, Volpe A, Genazzani AR. Studies on direct intraperitoneal insemination in the management of male factor, cervical factor, unexplained and immunological infertility. Hum Reprod. 1992;7: Abyholm T, Tanbo T, Dale PO, Magnus O. In vivo fertilization procedures in infertile women with patent fallopian tubes: a comparison of gamete intra-fallopian transfer, combined intrauterine and intraperitoneal insemination, and controlled ovarian hyperstimulation alone. J Assist Reprod Genet 1992;9: Yaniz JL, Lopez-Bejar M, Santolaria P, Rutllant J, Lopez-Gatius F. Intraperitoneal insemination in mammals: a review. Reprod Domest Anim 2002;37: Ajossa S, Melis GB, Cianci A, Coccia ME, Fulghesu AM, Giuffrida G, et al. An open multicenter study to compare the efficacy of intraperitoneal insemination and intrauterine insemination following multiple follicular development as treatment for unexplained infertility. J Assist Reprod Genet 1997;14: Sills ES, Palermo GD. Intrauterine pregnancy following low-dose gonadotropin ovulation induction and direct intraperitoneal insemination for severe cervical stenosis. BMC Pregnancy Childbirth 2002;2: Mamas FSP or IUTPI? Vol. 85, No. 3, March 2006