Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2006 Jan 25;2006(1):CD004635.
doi: 10.1002/14651858.CD004635.pub2.

Long-term pituitary down-regulation before in vitro fertilization (IVF) for women with endometriosis

Affiliations
Meta-Analysis

Long-term pituitary down-regulation before in vitro fertilization (IVF) for women with endometriosis

H N Sallam et al. Cochrane Database Syst Rev. .

Abstract

Background: Women with endometriosis who are treated with in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) have a lower pregnancy rate compared to women with tubal factor infertility. It has been suggested that the administration of gonadotrophin releasing hormone (GnRH) agonists for a few months prior to IVF or ICSI increases the pregnancy rate.

Objectives: To determine the effectiveness of administering GnRH agonists for three to six months prior to IVF or ICSI in women with endometriosis.

Search strategy: We used computer searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the National Research Register (NRR) and the MDSG Specialised Register of controlled trials. We handsearched proceedings of annual meetings of the American Society for Reproductive Medicine (ASRM) and the European Society for Human Reproduction and Embryology (ESHRE). We reviewed lists of references in original research and review articles. We contacted experts in various countries to identify unpublished trials.

Selection criteria: We included randomised controlled trials using any GnRH agonist prior to IVF or ICSI to treat women with any degree of endometriosis diagnosed by laparoscopy or laparotomy

Data collection and analysis: Two independent review authors abstracted data (HNS and JGV). We sent e-mails to investigators to seek additional information. We assessed the validity of each study using the methods suggested in the Cochrane Handbook. The data were checked by the third review author (SD) and any disagreement was resolved by arbitration with the fourth review author (AA). We generated 2 x 2 tables for principal outcome measures. The Peto-modified Mantel-Haenszel technique was used to calculate odds ratios (OR) and assess statistical heterogeneity between studies.

Main results: Three randomised controlled trials (with 165 women) were included. The live birth rate per woman was significantly higher in women receiving the GnRH agonist compared to the control group (OR 9.19, 95% CI 1.08 to 78.22). However, this was based on one trial reporting "viable pregnancy" only. The clinical pregnancy rate per woman was also significantly higher (three studies: OR 4.28, 95% CI 2.00 to 9.15). The information on miscarriage rates came from two trials with high heterogeneity and, therefore, results of the meta-analysis were doubtful. The included studies provided insufficient data to investigate the effects of administration of GnRH agonists on multiple or ectopic pregnancies, fetal abnormalities or other complications.

Authors' conclusions: The administration of GnRH agonists for a period of three to six months prior to IVF or ICSI in women with endometriosis increases the odds of clinical pregnancy by fourfold. Data regarding adverse effects of this therapy on the mother or fetus are not available at present.

PubMed Disclaimer

Conflict of interest statement

None known

Figures

1.1
1.1. Analysis
Comparison 1: GnRH agonist versus no agonist before IVF or ICSI, Outcome 1: Live birth rate per woman
1.2
1.2. Analysis
Comparison 1: GnRH agonist versus no agonist before IVF or ICSI, Outcome 2: Clinical pregnancy rate per woman
1.3
1.3. Analysis
Comparison 1: GnRH agonist versus no agonist before IVF or ICSI, Outcome 3: Miscarriage rate per clinically pregnant woman
1.4
1.4. Analysis
Comparison 1: GnRH agonist versus no agonist before IVF or ICSI, Outcome 4: Miscarriage rate per woman randomised
1.5
1.5. Analysis
Comparison 1: GnRH agonist versus no agonist before IVF or ICSI, Outcome 5: Dose of FSH or HMG (ampoules)
1.6
1.6. Analysis
Comparison 1: GnRH agonist versus no agonist before IVF or ICSI, Outcome 6: Duration of FSH administration (days)
1.7
1.7. Analysis
Comparison 1: GnRH agonist versus no agonist before IVF or ICSI, Outcome 7: Number of oocytes per woman

Update of

  • doi: 10.1002/14651858.CD004635

References

References to studies included in this review

Dicker 1992 {published data only}
    1. Dicker D, Goldman JA, Levy T, Feldberg D, Ashkenazi J. The impact of long-term gonadotropin-releasing hormone analogue treatment on preclinical abortions in patients with severe endometriosis undergoing in vitro fertilization-embryo transfer. Fertility and Sterility 1992;57(3):597-600. [MEDLINE: ] - PubMed
Rickes 2002 {published data only}
    1. Rickes D, Nickel I, Kropf S, Kleinstein J. Increased pregnancy rates after ultralong postoperative therapy with gonadotropin-releasing hormone analogs in patients with endometriosis. Fertility and Sterility 2002;78(4):757-62. [MEDLINE: ] - PubMed
Surrey 2002 {published and unpublished data}
    1. Surrey ES, Silverberg KM, Surrey MW, Schoolcraft WB. Effect of prolonged gonadotropin-releasing hormone agonist therapy on the outcome of in vitro fertilization-embryo transfer in patients with endometriosis. Fertility and Sterility 2002;78(4):699-704. [MEDLINE: ] - PubMed

References to studies excluded from this review

Chedid 1995 {published data only}
    1. Chedid S, Camus M, Smitz J, Van Steirteghem AC, Devroey P. Comparison among different ovarian stimulation regimens for assisted procreation procedures in patients with endometriosis. Human Reproduction 1995;10(9):2406-11. - PubMed
Curtis 1993 {published data only}
    1. Curtis P, Jackson A, Bernard A, Shaw RW. Pretreatment with gonadotrophin releasing hormone (GnRH) analogue prior to in vitro fertilisation for patients with endometriosis. European Journal of Obstetrics, Gynecology and Reproductive Biology 1993;52(3):211-6. - PubMed
Dale 1990 {published data only}
    1. Dale PO, Tanbo T, Abyholm T. Endometriosis-associated infertility treated by long-term gonadogropin-releasing hormone agonist administration and assisted fertilization. Journal of In Vitro Fertilisation and Embryo Transfer 1990;7(3):180-1. - PubMed
Dicker 1990 {published data only}
    1. Dicker D, Goldman GA, Ashkenazi J, Feldberg D, Violiovitz I, Goldman JA. The value of pretreatment with gonadotrophin releasing hormone (GnRH) analogue in IVF-ET therapy of severe endometriosis. Human Reproduction 1990;5(4):418-20. [MEDLINE: ] - PubMed
Fabregues 1998 {published data only}
    1. Fabregues F, Balasch J, Creus M, Civico S, Carmona F, Puerto B, Vanrell JA. Long-term down-regulation does not improve pregnancy rates in an in vitro fertilization program. Fertility and Sterility 1998;70(1):46-51. [MEDLINE: ] - PubMed
Marcus 1994 {published data only}
    1. Marcus SF, Edwards RG. High rates of pregnancy after long-term down-regulation of women with severe endometriosis. American Journal of Obstetrics and Gynecology 1994;171(3):812-7. - PubMed
Nakagawa 2000 {published data only}
    1. Nakagawa K, Yamano S, Nakasaka H, Komatsu J, Hinokio K, Aono T. Effectiveness of pre-treatment with gonadotropin-releasing hormone agonist to patients with endometriosis in in-vitro fertilization and embryo transfer. Japanese Journal of Fertility and Sterility 2000;45(1):1-6.
Nakamura 1992 {published data only}
    1. Nakamura K, Oosawa M, Kondou I, Inagaki S, Shibata H, Narita O, et al. Menotropin stimulation after prolonged gonadotropin releasing hormone agonist pretreatment for in vitro fertilization in patients with endometriosis. Journal of Assisted Reproduction and Genetics 1992;9(2):113-7. - PubMed
Oehninger 1989 {published data only}
    1. Oehninger S, Brzyski RG, Mausher SJ, Acosta AA, Jones GS. In-vitro fertilization and embryo transfer in patients with endometriosis: impact of a gonadotrophin releasing hormone agonist. Human Reproduction 1989;4(5):541-4. - PubMed
Ruiz‐Velasco 1998 {published data only}
    1. Ruiz-Velasco V, Allende S. Goserelin followed by assisted reproduction: results in infertile women with endometriosis. International Journal of Fertility and Women's Medicine 1998;43(1):18-23. - PubMed
Sahebkashaf 2003 {published data only}
    1. Sahebkashaf H, Aleyassin A, Saidi H, Ghalavand N, Adel HG, Sahebkashaf H. Effect of prolonged gonadotropin-releasing hormone agonist therapy on the outcome of rapid ICSI-ZIFT in patients with endometriosis. In: Fertility and Sterility. Vol. 80. 2003:S121. [10.1016/s0015-0282(03)01191-9]

Additional references

Aboulghar 2003
    1. Aboulghar MA, Mansour RT, Serour GI, Al-Inany HG, Aboulghar MM. The outcome of in vitro fertilization in advanced endometriosis with previous surgery: a case-controlled study. American Journal of Obstetrics and Gynecology 2003;188(2):371-5. - PubMed
Arici 1996
    1. Arici A, Oral E, Bukulmez O, Duleba A, Olive DL, Jones EE. The effect of endometriosis on implantation: results from the Yale University in vitro fertilization and embryo transfer program. Fertility and Sterility 1996;65(3):603-7. - PubMed
Barnhart 2002
    1. Barnhart K, Dunsmoor-Su R, Coutifaris C. Effect of endometriosis on in vitro fertilization. Fertility and Sterility 2002;77(6):1148-55. - PubMed
Bergendal 1998
    1. Bergendal A, Naffah S, Nagy C, Bergqvist A, Sjoblom P, Hillensjo T. Outcome of IVF in patients with endometriosis in comparison with tubal-factor infertility. Journal of Assisted Reproduction and Genetics 1998;15(9):530-4. - PMC - PubMed
Cahill 1997
    1. Cahill DJ, Wardle PG, Maile LA, Harlow CR, Hull MG. Ovarian dysfunction in endometriosis-associated and unexplained infertility. Journal of Assisted Reproduction and Genetics 1997;14(10):554-7. - PMC - PubMed
Canis 2001
    1. Canis M, Pouly JL, Tamburro S, Mage G, Wattiez A, Bruhat MA. Ovarian response during IVF-embryo transfer cycles after laparoscopic ovarian cystectomy for endometriotic cysts of >3 cm in diameter. Human Reproduction 2001;16(12):2583-6. - PubMed
Carlberg 2000
    1. Carllberg M, Nejaty J, Froysa B, Guan Y, Soder O, Bergqvist A. Elevated expression of tumour necrosis factor alpha in cultured granulosa cells from women with endometriosis. Human Reproduction 2000;15(6):1250-5. - PubMed
CONSORT
    1. Moher D, Schultz KF, Altman DG. The CONSORT statement: revised recommendations for improving the quality of reports of parallel group randomised trials. The Lancet 2001;357:1191-4. - PubMed
Cunha‐Filho 2003
    1. Cunha-Filho JS, Lemos NA, Freitas FM, Faller M, Passos EP. Insulin-like growth factor (IGF)-1 and IGF binding protein-1 and -3 in the follicular fluid of infertile patients with endometriosis. Human Reproduction 2003;18(2):423-8. - PubMed
Dicker 1991
    1. Dicker D, Goldman JA, Feldberg D, Ashkenazi J, Levy T. Transvaginal ultrasonic needle-guided aspiration of endometriotic cysts before ovulation induction for in vitro fertilization. Journal of In Vitro Fertilisation and Embryo Transfer 1991;8(5):286-9. - PubMed
Dicker 1993
    1. Dicker D, Ashkenazi J, Feldberg D, Levy T, Dekel A, Ben-Rafael Z. Severe abdominal complications after transvaginal ultrasonographically guided retrieval of oocytes for in vitro fertilization and embryo transfer. Fertility and Sterility 1993;59(6):1313-5. - PubMed
Dmowski 1995
    1. Dmowski WP, Rana N, Michalowska J, Friberg J, Papierniak C, el-Roely A. The effect of endometriosis, its stage and activity, and of autoantibodies on in vitro fertilization and embryo transfer success rates. Fertility and Sterility 1995;63(3):555-62. - PubMed
Donnez 2001
    1. Donnez J, Wyns C, Nisolle M. Does ovarian surgery for endometriomas impair the ovarian response to gonadogropin? Fertility and Sterility 2001;76(4):662-5. - PubMed
Frydman 1987
    1. Frydman R, Belaisch-Allart JC. Results of in vitro fertilization for endometriosis. Contribution to Gynecology and Obstetrics 1987;16:328-36. - PubMed
Garcia‐Velasco 2002
    1. Garcia-Velasco JA, Mulayim N, Kayisli UA, Arici A. Elevated soluble Fas ligand levels may suggest a role for apoptosis in women with endometriosis. Fertility and Sterility 2002;78(4):855-9. - PubMed
Garrido 2000
    1. Garrido N, Nevarro J, Remohi J, Simon C, Pellicer A. Follicular hormonal environment and embryo quality in women with endometriosis. Human Reproduction Update 2000;6(1):67-74. - PubMed
Gerber 1995
    1. Gerber S, Paraschos T, Atkinson G, Margara R, Winston RM. Results of IVF in patients with endometriosis: the severity of the disease does not affect outcome, or incidence of miscarriage. Human Reproduction 1995;10(6):1507-11. - PubMed
Gerber 2002
    1. Gerber S, Ferreira DP, Spyer Prates LF, Sales L, Sampaio M. Effects of previous ovarian surgery for endometriosis on the outcome of assisted reproduction treatment. Reproductive Biomedicine Online 2002;5(2):162-6. - PubMed
Hickman 2002
    1. Hickman TN. Impact of endometriosis on implantation. Data from the Wilford Hall Medical Centre IVF-ET Program. Journal of Reproductive Medicine 2002;47(10):801-8. - PubMed
Ho 2002
    1. Ho HY, Lee RK, Hwu YM, Su JT, Tsai YC. Poor response of ovaries with endometrioma previously treated with cystectomy to controlled ovarian hyperstimulation. Journal of Assisted Reproduction and Genetics 2002;19(11):507-11. - PMC - PubMed
Huang 1997
    1. Huang HY, Lee CL, Lai YM, Chang MY, Soong YK. The outcome of in vitro fertilization and embryo transfer therapy in women with endometriosis failing to conceive after laparoscopic conservative surgery. Journal of the American Association of Gynecologic Laparoscopists 1997;4(3):299-303. - PubMed
Hull 1998
    1. Hull MG, Williams JA, Ray B, McLaughlin EA, Akande VA, Ford WC. The contribution of suble oocyte or sperm dysfunction affecting fertilization in endometriosis-associated or unexplained infertility: a controlled comparison with tubal infertility and use of donor spermatozoa. Human Reproduction 1998;13(7):1825-30. - PubMed
Inoue 1992
    1. Inoue M, Kobayashi Y, Honda I, Awaji H, Fujii A. The impact of endometriosis on the reproductive outcome of infertile patients. American Journal of Obstetrics and Gynecology 1992;167(1):278-82. - PubMed
Kim 1997
    1. Kim CH, Chae HD, Kang BM, Chang YS, Mok JE. The immunotherapy during in vitro fertilization and embryo transfer cycles in infertile patients with endometriosis. Journal of Obstetric and Gynaecologic Research 1997;23(5):463-70. - PubMed
Mahadevan 1983
    1. Mahadevan MM, Trounson AO, Leeton JF. The relationship of tubal blockage, infertility of unknown cause, suspected male infertility, and endometriosis to success of in vitro fertilization and embryo transfer. Fertility and Sterility 1983;40(6):755-62. - PubMed
Marconi 2002
    1. Marconi G, Vilela M, Quintana R, Sueldo C. Laparoscopic ovarian cystectomy of endometriomas does not affect the ovarian response to gonadotropin stimulation. Fertility and Sterility 2002;78(4):876-8. - PubMed
Matson 1986
    1. Matson PL, Yovich JL. The treatment of infertility associated with endomentriosis by in vitro fertilization. Fertility and Sterility 1986;46(3):432-4. - PubMed
Mills 1992
    1. Mills MS, Eddowes HA, Cahill DJ, Fahy UM, Abuzeid MU, McDermott A, et al. A prospective controlled study of in-vitro fertilization, gamete intra-fallopian transfer and intrauterine insemination combined with superovulation. Human Reproduction 1992;7(4):490-4. - PubMed
Nakahara 1998
    1. Nakahara K, Saito H, Saito T, Ito M, Ohta N, Takahashi T, et al. Ovarian fecundity in patients with endometriosis can be estimated by the incidence of apoptotic bodies. Fertility and Sterility 1998;69(5):931-5. - PubMed
Nargund 1995
    1. Nargund G, Parsons J. Infected endometriotic cysts secondary to oocyte aspiration for in-vitro fertilization. Human Reproduction 1995;10(6):1555. - PubMed
Norenstedt 2001
    1. Norenstedt SN, Linderoth-Nagy C, Bergendal A, Sjoblom P, Bergqvist A. Reduced developmental potential in oocytes from women with endometriosis. Journal of Assisted Reproduction and Genetics 2001;18(12):644-9. - PMC - PubMed
O'Shea 1985
    1. O'Shea RT, Chen C, Weiss T, Jones WR. Endometriosis and in-vitro fertilisation. Lancet 1985;2(8457):723. - PubMed
Olivennes 1995
    1. Olivennes F, Feldberg D, Lui HC, Cohen J, Moy F, Rosenwaks Z. Endometriosis: a stage by stage analysis - the role of in vitro fertilization. Fertility and Sterility 1995;64(2):392-8. - PubMed
Padigas 1996
    1. Pagidas K, Falcone T, Hemmings R, Miron P. Comparison of reoperation for moderate (stage III) and severe (stage IV) endometriosis-related infertility with in vitro fertilization-embryo transfer. Fertility and Sterility 1996;65(4):791-5. - PubMed
Padila 1993
    1. Padilla SL. Ovarian abscess following puncture of an endometrioma during ultrasound-guided oocyte retrieval. Human Reproduction 1993;8(8):1282-3. - PubMed
Pal 1998
    1. Pal L, Shifren JL, Isaacson KB, Chang Y, Leykin L, Toth TL. Impact of varying stages of endometriosis on the outcome of in vitro fertilization-embryo transfer. Journal of Assisted Reproduction and Genetics 1998;15(1):27-31. - PMC - PubMed
Pellicer 1998a
    1. Pellicer A, Valbuena D, Bauset C, Albert C, Bonilla-Musoles F, Remohi J, et al. The follicular endocrine environment in stimuated cycles of women with endometriosis: steroid levels and embryo quality. Fertility and Sterility 1998;69(6):1135-41. - PubMed
Pellicer 1998b
    1. Pellicer A, Albert C, Mercader A, Bonilla-Musoles F, Remohi J, Simon C. The follicular and endocrine environment in women with endometriosis: local and systemic cytokine production. Fertility and Sterility 1998;70(3):425-31. - PubMed
Pellicer 2001
    1. Pellicer A, Navarro J, Bosch E, Garrido N, Garcia-Velasco JA, Remohi J, et al. Endometrial quality in infertile women with endometriosis. Annals of the New York Academy of Science 2001;943:122-30. - PubMed
Simon 1994
    1. Simon C, Gutierrez A, Vidal A, los Santos MJ, Tarin JJ, Remohi J, et al. Outcome of patients with endometriosis in assisted reproduction: results from in-vitro fertilization and oocyte donation. Human Reproduction 1994;9(4):725-9. - PubMed
Smith 2002
    1. Smith MP, Keay SD, Margo FC, Harlow CR, Wood PJ, Cahill DJ, et al. Total cortisol levels are reduced in the periovulatory follicle of infertile women with minimal-mild endometriosis. American Journal of Reproductive Immunology 2002;47(1):52-6. - PubMed
Suganuma 2002
    1. Suganuma N, Wakahara Y, Ishida D, Asano M, Kitagawa T, Katsumata Y, et al. Pretreatment for ovarian endometrial cyst before in vitro fertilization. Gynecologic and Obstetric Investigations 2002;54 Suppl(1):36-40. - PubMed
Sung 1997
    1. Sung L, Mukherjee T, Takeshige T, Bustillo M, Copperman AB. Endometriosis is not detrimental to embryo implantation in oocyte recipients. Journal of Assisted Reproduction and Genetics 1997;14(3):152-6. - PMC - PubMed
Suzuki 2005
    1. Suzuki T, Izumi S, Matsubayashi H, Awaji H, Yoshikata K, Makino T. Impact of ovarian endometrioma on oocytes and pregnancy outcome in in-vitro fertilization. Fertility and Sterility 2005;83(4):908-13. [MEDLINE: ] - PubMed
Tanbo 1995
    1. Tanbo T, Omland A, Dale PO, Abyholm T. In vitro fertilization/embryo transfer in unexplained infertility and minimal peritoneal endometriosis. Acta Obstetrica Gynecologica Scandinavia 1995;74(7):539-43. - PubMed
Tei 1998
    1. Tei C, Miyazaki T, Kuji N, Tanaka M, Sueoka K, Yoshimura Y. Effect of danazol on the pregnancy rate in patients with unsuccessful in vitro fertilization-embryo transfer. Journal of Reproductive Medicine 1998;43(6):541-6. - PubMed
Toya 2000
    1. Toya M, Saito H, Ohta N, Saito T, Kaneko T, Hiroi M. Moderate and severe endometriosis is associated with alterations in the cell cycle of granulosa cells in patients undergoing in vitro fertilization and embryo transfer. Fertility and Sterility 2000;73(2):344-50. - PubMed
Wardle 1985
    1. Wardle PG, Mitchell JD, McLaughlin EA, Ray BD, McDermott A, Hull MG. Endometriosis and ovulatory disorder: reduced fertilisation in vitro compared with tubal and unexplained infertility. Lancet 1985;2(8449):236-9. - PubMed
Wei 1998
    1. Wei CF, Chen SC. Pelvic abscess after ultrasound-guided aspiration of endometrioma: a case report. Zhonghua Yi Xue Za Zhi (Taipei) 1998;61(10):603-7. - PubMed
Wyns 2003
    1. Wyns C, Donnez J. Laser vaporization of ovarian endometriomas: the impact on the response to gonadotrophin stimulation. Gynecologie, Obstetrique, Fertilite (French) 2003;31(4):337-42. - PubMed
Yaron 1994
    1. Yaron Y, Peyser MR, Samuel D, Amit A, Lessing JB. Infected endometriotic cysts secondary to oocyte aspiration for in-vitro fertilization. Human Reproduction 1994;9(9):1759-60. - PubMed
Younis 1997
    1. Younis JS, Ezra Y, Laufer N, Ohel G. Late manifestation of pelvic abscess following oocyte retrieval, for in vitro fertilization, in patients with severe endometriosis and ovarian endometriomata. Journal of Assisted Reproduction and Genetics 1997;14(6):343-6. - PMC - PubMed
Yovich 1985
    1. Yovich JL, Yovich JM, Tuvik AI, Matson PL, Willcox DL. In-vitro fertilisation for endometriosis. Lancet 1985;7(2 (8454)):552. - PubMed

MeSH terms

Substances