Intrauterine Insemination unter Gonadotropin-Stimulation im GnRH-Antagonisten - Protokoll in einem evidenzbasiert selektierten Patientenkollektiv

Zusammenfassung

In prospektiver Art wurden 64 Patientinnen nach einem standardisierten Protokoll ausgewählt und in 133 Inseminationszyklen behandelt. Das durchschnittliche Alter betrug 33,05 ± 3,92 Jahre bei einer mittleren Kinderwunschdauer von 2,63 ± 1,49 Jahren. Etwa ⅔ der Patientinnen wiesen eine primäre Sterilität auf. Es konnten 32 Schwangerschaften erzielt werden. Die kumulative Schwangerschaftsrate pro Patientin lag bei 41 %, die kumulative weiterlaufende Schwangerschaftsrate bei 30 %. Unabhängig davon, ob ein Tubenfaktor per laparoscopiam abgeklärt und unauffällig war, oder aber ob aufgrund der vorangehenden Anamnese ein Tubenfaktor unwahrscheinlich war, unterschied sich die Schwangerschaftsrate nicht. Somit kann in individuellen Fällen - bei komplettem Fehlen von Risikofaktoren - offenbar auf die in jedem Falle durchgeführte Laparoskopie verzichtet werden. Die Spermienzahlen im Nativejakulat vor Insemination spielten keine Rolle für den Erfolg. Wesentlich war die Absolutzahl der progressiv motilen Spermien (nach WHO A und B) im aufbereiteten Ejakulat, die einen signifikanten Einfluss auf das Eintreten einer Schwangerschaft hatten. Das Stimulationsprotokoll mit rekombinantem humanen (r-h)FSH in einem Pen (Puregon Pen) unter gleichzeitiger Verwendung eines GnRH-Antagonisten (Cetrotide® 0,25 mg) im Mehrfachdosisprotokoll erlaubte ein optimales Timing der Insemination. Zusammenfassend kann also die gezielte Patientenselektion unter Einsatz innovativer Stimulationsverfahren einen hohen Erfolg in der Inseminationsbehandlung garantieren helfen. Dies gibt der Inseminationsbehandlung einen gerechtfertigten Stellenwert in der Behandlung des Kinderwunschpaares.

Abstract

Sixty-four patients were prospectively counselled and selected for intrauterine insemination. All patients were counselled and selected based on a standardized scheme and treated over 133 insemination cycles. Mean age was 33.05 ± 3.92 years with a mean duration of infertility of 2.63 ± 1.49 years. Around ⅔ of patients suffered from primary infertility. 32 pregnancies could be established. The cumulative pregnancy rate was 41 % per patient, the cumulative ongoing pregnancy rate was 30 %. The pregnancy rate was comparable, irrespective of whether a tubal factor had been excluded by laparoscopy or not, as no previously known factors were present which presented as a tubal risk factor. Therefore, in individual cases - when there is complete absence of risk factors for tubal infertility - it is possible to skip the laparoscopy. The sperm count before semen preparation did not influence the success rate. The absolute number of progressively motile sperms (WHO A and B), however, had a significant influence on success rates. The stimulation protocol always included recombinant human (r-h)FSH in a pen device (Puregon Pen). All stimulation procedures were done using a multiple dose antagonist protocol with 0.25 mg daily Cetrotide®. This allowed optimal timing of intrauterine insemination after hCG administration (around 4 - 6 hours before ovulation) and contributed significantly to the success rate in this cohort of patients. In conclusion, the evidence-based selection of patients as well as the use of innovative stimulation protocols makes intrauterine insemination a very successful treatment. Intrauterine insemination, therefore, has its place in infertility treatment.

Schlüsselwörter

Intrauterine Insemination - rekombinantes humanes FSH - GnRH-Antagonist

Key words

Intrauterine insemination - recombinant human FSH - GnRH antagonist

Literatur

• 1 Goverde A J, McDonnell J, Vermeiden J P, Schats R, Rutten F FH, Schoemaker J. Intrauterine insemination or in-vitro fertilisation in idiopathic subfertility and male subfertility: a randomised trial and cost-effectiveness analysis.  Lancet. 2000;  355 13-18
• 2 Schröder A K, Banz C, Diedrich K, Ludwig M. Intrauterine Insemination - eine Übersicht.  Reproduktionsmedizin. 2002;  18 313-326
• 3 Hughes E G. The effectiveness of ovulation induction and intrauterine insemination in the treatment of persistent infertility: a meta-analysis.  Hum Reprod. 1997;  12 1865-1872
• 4 Khalil M R, Rasmussen P E, Erb K, Laursen S B, Rex S, Westergaard L G. Homologous intrauterine insemination. An evaluation of prognostic factors based on a review of 2473 cycles.  Acta Obstet Gynecol Scand. 2001;  80 74-81
• 5 Prietl G, Haidl G, Krebs D. Sterilitätsbehandlung durch homologe intrauterine Insemination.  Reproduktionsmedizin. 2000;  16 376-383
• 6 Cantineau A E, Heineman M J, Cohlen B J. Single versus double intrauterine insemination in stimulated cycles for subfertile couples: a systematic review based on a Cochrane review.  Hum Reprod. 2003;  18 941-946
• 7 Dunson D B, Colombo B, Baird D D. Changes with age in the level and duration of fertility in the menstrual cycle.  Hum Reprod. 2002;  17 1399-1403
• 8 Wilcox A J, Weinberg C R, Baird D D. Timing of sexual intercourse in relation to ovulation. Effects on the probability of conception, survival of the pregnancy, and sex of the baby.  N Engl J Med. 1995;  333 1517-1521
• 9 Aboulghar M, Mansour R, Serour G, Abdrazek A, Amin Y, Rhodes C. Controlled ovarian hyperstimulation and intrauterine insemination for treatment of unexplained infertility should be limited to a maximum of three trials.  Fertil Steril. 2001;  75 88-91
• 10 Aboulghar M A, Mansour R T, Serour G I, Amin Y, Abbas A M, Salah I M. Ovarian superstimulation and intrauterine insemination for the treatment of unexplained infertility.  Fertil Steril. 1993;  60 303-306
• 11 Sahakyan M, Harlow B L, Hornstein M D. Influence of age, diagnosis, and cycle number on pregnancy rates with gonadotropin-induced controlled ovarian hyperstimulation and intrauterine insemination.  Fertil Steril. 1999;  72 500-504
• 12 Dickey R P, Taylor S N, Lu P Y, Sartor B M, Rye P H, Pyrzak R. Effect of diagnosis, age, sperm quality, and number of preovulatory follicles on the outcome of multiple cycles of clomiphene citrate-intrauterine insemination.  Fertil Steril. 2002;  78 1088-1095
• 13 Dickey R P, Olar T T, Taylor S N, Curole D N, Rye P H, Matulich E M. Relationship of follicle number, serum estradiol, and other factors to birth rate and multiparity in human menopausal gonadotropin-induced intrauterine insemination cycles.  Fertil Steril. 1991;  56 89-92
• 14 Evers J LH. Female subfertility.  Lancet. 2002;  360 151-159
• 15 Tanahatoe S, Hompes P G, Lambalk C B. Accuracy of diagnostic laparoscopy in the infertility work-up before intrauterine insemination.  Fertil Steril. 2003;  79 361-366
• 16 Aytoz A, Tournaye H, Camus M, Ubaldi F, Verheyen G, Van Steirteghem A. et al . Is there any need for diagnostic laparoscopy in couples undergoing intracytoplasmic sperm injection for severe male-factor infertility.  J Assist Reprod Genet. 1998;  15 79-83
• 17 Rickes D, Nickel I, Kropf S, Kleinstein J. Increased pregnancy rates after ultralong postoperative therapy with gonadotropin-releasing hormone analogs in patients with endometriosis.  Fertil Steril. 2002;  78 757-762
• 18 Surrey E S, Silverberg K M, Surrey M W, Schoolcraft W B. Effect of prolonged gonadotropin-releasing hormone agonist therapy on the outcome of in vitro fertilization-embryo transfer in patients with endometriosis.  Fertil Steril. 2002;  78 699-704
• 19 Capelo F O, Kumar A, Steinkampf M P, Azziz R. Laparoscopic evaluation following failure to achieve pregnancy after ovulation induction with clomiphene citrate.  Fertil Steril. 2003;  80 1450-1453
• 20 Donnez J, Jadoul P. Taking a history in the evaluation of infertility: obsolete or venerable tradition?.  Fertil Steril. 2004;  81 16-17
• 21 Tulandi T, Platt R. The art of taking a history.  Fertil Steril. 2004;  81 11-12
• 22 Hubacher D, Grimes D, Lara-Ricalde R, de la J J, Garcia-Luna A. The limited clinical usefulness of taking a history in the evaluation of women with tubal factor infertility.  Fertil Steril. 2004;  81 6-10
• 23 Dickey R P, Pyrzak R, Lu P Y, Taylor S N, Rye P H. Comparison of the sperm quality necessary for successful intrauterine insemination with World Health Organization threshold values for normal sperm.  Fertil Steril. 1999;  71 684-689
• 24 Cohlen B J, Te Velde E R, Van Kooij R J, Looman C W, Habbema J D. Controlled ovarian hyperstimulation and intrauterine insemination for treating male subfertility: a controlled study.  Hum Reprod. 1998;  13 1553-1558
• 25 Khalil M R, Rasmussen P E, Erb K, Laursen S B, Rex S, Westergaard L G. Intrauterine insemination with donor semen. An evaluation of prognostic factors based on a review of 1131 cycles.  Acta Obstet Gynecol Scand. 2001;  80 342-348
• 26 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;  14 698-703
• 27 Ombelet W, Vandeput H, Van de P G, Cox A, Janssen M, Jacobs P. et al . Intrauterine insemination after ovarian stimulation with clomiphene citrate: predictive potential of inseminating motile count and sperm morphology.  Hum Reprod. 1997;  12 1458-1463
• 28 Campana A, Sakkas D, Stalberg A, Bianchi P G, Comte I, Pache T. et al . Intrauterine insemination: evaluation of the results according to the woman's age, sperm quality, total sperm count per insemination and life table analysis.  Hum Reprod. 1996;  11 732-736
• 29 Van Voorhis B J, Barnett M, Sparks A E, Syrop C H, Rosenthal G, Dawson J. Effect of the total motile sperm count on the efficacy and cost-effectiveness of intrauterine insemination and in vitro fertilization.  Fertil Steril. 2001;  75 661-668
• 30 Gleicher N, Oleske D M, Tur-Kaspa I, Vidali A, Karande V. Reducing the risk of high-order multiple pregnancy after ovarian stimulation with gonadotropins.  N Engl J Med. 2000;  343 2-7
• 31 De Geyter C, De Geyter M, Castro E, Bals-Pratsch M, Nieschlag E, Schneider H P. Experience with transvaginal ultrasound-guided aspiration of supernumerary follicles for the prevention of multiple pregnancies after ovulation induction and intrauterine insemination.  Fertil Steril. 1996;  65 1163-1168
• 32 Dickey R P, Taylor S N, Lu P Y, Sartor B M, Rye P H, Pyrzak R. Relationship of follicle numbers and estradiol levels to multiple implantation in 3, 608 intrauterine insemination cycles.  Fertil Steril. 2001;  75 69-78
• 33 Dickey R P, Olar T T, Taylor S N, Curole D N, Rye P H. Relationship of follicle number and other factors to fecundability and multiple pregnancy in clomiphene citrate-induced intrauterine insemination cycles.  Fertil Steril. 1992;  57 613-619
• 34 Ludwig M, Kohl M, Krüger A, Löning M, Schröder A K, Katalinic A. et al . Komplikationen bei höhergradigen Mehrlingsschwangerschaften für Mutter und Kind.  Geburtsh Frauenheilk. 2004;  64 168-177
• 35 Schröder A K, Schroers U, Katalinic A, Diedrich K, Ludwig M. Mehrlingsrisiko nach assistierter Reproduktion - Einschätzung des Risikos durch Betroffene und Nichtbetroffene.  Geburtsh Frauenheilk. 2003;  63 356-363
• 36 Fuh K W, Wang X, Tai A, Wong I, Norman R J. Intrauterine insemination: effect of the temporal relationship between the luteinizing hormone surge, human chorionic gonadotrophin administration and insemination on pregnancy rates.  Hum Reprod. 1997;  12 2162-2166
• 37 Ludwig M, Katalinic A, Diedrich K. Use of GnRH antagonists in ovarian stimulation for ART compared to the long protocol: a meta-analysis.  Arch Gynecol Obstet. 2001;  265 175-182
• 38 Nuojua-Huttunen S, Gissler M, Martikainen H, Tuomivaara L. Obstetric and perinatal outcome of pregnancies after intrauterine insemination.  Hum Reprod. 1999;  14 2110-2115