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22 - Ovulation Induction

from PART II - INFERTILITY EVALUATION AND TREATMENT

Published online by Cambridge University Press:  04 August 2010

By
Evert J. P. Van Santbrink  and
Bart C. J. M. Fauser
Edited by
Botros R. M. B. Rizk ,
Juan A. Garcia-Velasco ,
Hassan N. Sallam  and
Antonis Makrigiannakis
Botros R. M. B. Rizk
Affiliation:
University of South Alabama
Juan A. Garcia-Velasco
Affiliation:
Rey Juan Carlos University School of Medicine,
Hassan N. Sallam
Affiliation:
University of Alexandria School of Medicine
Antonis Makrigiannakis
Affiliation:
University of Crete
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Summary

INTRODUCTION

Primary treatment of patients presenting with infertility and chronic anovulation aims at restoring normal physiology, that is, selection of a single dominant follicle followed by mono-ovulation (ESHRE Capri Workshop Group, 2003). This process is generally referred to as “ovulation induction.” Alternative protocols for ovarian stimulation used in fertility treatment are (controlled) ovarian hyperstimulation used for intrauterine insemination or in vitro fertilization (IVF). These treatment protocols are aimed at the development of multiple instead of one dominant follicle and thereby result in a nonphysiological condition.

Anovulation is a relatively common problem in the infertility population (approximately, 21 percent of fertility couples; Hull et al., 1985), and it may be considered an absolute factor to prevent pregnancy. Treatment results may be expected to be very good when normoovulatory cycles are restored, in the absence of concomitant fertility problems.

Classification of anovulation is generally based on the combination of a menstrual cycle disturbance (oligo- or amenorrhea) and laboratory findings (Insler et al., 1968; Rowe et al., 1993). The majority of anovulatory patients (about 80 percent, Rowe et al., 1993) will have normal serum concentrations of estradiol (E2) and follicle-stimulating hormone (FSH) and a small proportion (approximately 10 percent) decreased concentrations of both hormones (WHO2 and WHO1, respectively according to the WHO-classification). The remaining group (approximately 10 percent) may be classified as WHO3 and they present with elevated FSH combined along with decreased E2 concentrations resulting in anovulation caused by (imminent) ovarian failure or premature ovarian aging.

Keywords

antiestrogensaromatase inhibitorsdopamine agonistsgonadotropinsnormogonadotropic anovulationlaparoscopic electrocauteryovulation inductionhypogonadotropic anovulation
Type
Chapter
Information
Infertility and Assisted Reproduction , pp. 193 - 201
Publisher: Cambridge University Press
Print publication year: 2008

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References

Aboulghar, M.A. and Mansour, R.T. (2006). Ovarian hyperstimulation syndrome: classifications and critical analysis of preventive measures. Human Reproduction Update, 9, 275–289.CrossRefGoogle Scholar
Amer, S.A., Li, T.C. and Ledger, W.L. (2004). Ovulation induction using laparoscopic ovarian drilling in women with PCOS: predictors of success. Human Reproduction, 19, 1719–1724.CrossRefGoogle ScholarPubMed
Bayar, U., Basaran, M., Kiran, S., Coskun, A. and Gezer, S. (2006). Use of an aromatase inhibitor in patients with polycystic ovary syndrome: a prospective randomized trial. Fertility and Sterility, 86, 1447–1451.CrossRefGoogle ScholarPubMed
Bayram, N., Wely, M., Kaayk, E.M., Bossuyt, P.M. and Veen, F. (2004). Using an electrocautery strategy or recombinant follicle stimulating hormone to induce ovulation in polycystic ovary syndrome: randomised controlled trial. British Medical Journal, 328, 192–195.CrossRefGoogle ScholarPubMed
Beckers, N.G., Platteau, P., Eijkemans, M.J., Macklon, N.S., Jong, F.H., Devroey, P. and Fauser, B.C. (2006). The early luteal phase administration of estrogen and progesterone does not induce premature luteolysis in normo-ovulatory women. European Journal of Endocrinology, 155, 355–363.CrossRefGoogle Scholar
Boostanfar, R., Jain, J.K., Nishell, D.R. and Paulson, R.J. (2001). A prospective randomized trial comparing clomiphene citrate with tamoxifen citrate for ovulation induction. Fertility and Sterility, 75, 1024–1026.CrossRefGoogle ScholarPubMed
Brown, J.B. (1978) Pituitary control of ovarian function – concepts derived from gonadotropin therapy. The Australian and New Zealand Journal Obstetrics and Gynecology, 18, 47–54.CrossRefGoogle Scholar
Christin-Maitre, S. and Hugues, J.N. (2003). A comparative randomized multicentric study comparing the step-up versus step-down protocol in polycystic ovary syndrome. Human Reproduction, 18, 1626–1631.CrossRefGoogle ScholarPubMed
Clark, A.M., Thornley, B., Tomlinson, L., Galletley, C. and Norman, R.J. (1998). Weight loss in obese infertile women results in improvement of reproductive outcome for all forms of fertility treatment. Human Reproduction, 13, 1502–1505.CrossRefGoogle ScholarPubMed
Coffler, M.S., Patel, K., Dahan, M.H., Yoo, R.Y., Malcom, P.J. and Chang, R.J. (2003). Enhanced granulosa cell responsiveness to FSH during insulin infusion in women with PCOS treated with pioglitazone. Journal of Clinical Endocrinology and Metabolism, 88, 5624–5631.CrossRefGoogle ScholarPubMed
Costello, M.F. and Eden, J.A. (2003). A systematic review of the reproductive system effects of metformin in patients with PCOS. Fertility and Sterility, 79, 1–13.CrossRefGoogle Scholar
Couzinet, B., Young, J., Brailly, S., Chanson, P. and Schaison, G. (1995). Even after priming with ovarian steroids or pulsatile gonadotropin-releasing hormone administration, naltrexon is unable to induce ovulation in women with functional hypothalamic amenorrhea. Journal of Clinical Endocrinology and Metabolism, 80, 2102–2107.Google ScholarPubMed
Dehbashi, S., Vafaei, H., Parsanezhad, M.D. and Alborzi, S. (2006). Time of initiation of clomiphene citrate and pregnancy rate in polycystic ovarian syndrome. International Journal of Gynaecology and Obstetrics, 93, 44–48.CrossRefGoogle ScholarPubMed
Dobson, H., Ghuman, S., Prabhakar, S. and Smith, R. (2003). A conceptual model of the influence of stress on female reproduction. Reproduction, 125, 151–163.CrossRefGoogle ScholarPubMed
Eijkemans, M.J., Imani, B., Mulders, A.G., Habbema, J.D. and Fauser, B.C. (2005). High singleton live birth rate following classical ovulation induction in normogonadotropic anovulatory infertility. Human Reproduction, 18, 2357–2362.CrossRefGoogle Scholar
Eijkemans, M.J., Polinder, S., Mulders, A.G., Laven, J.S., Habbema, J.D. and Fauser, B.C. (2005). Individualized cost-effective conventional ovulation induction treatment in normogonadotrophic anovulatory infertility (WHO2). Human Reproduction, 20, 2830–2837.CrossRefGoogle Scholar
ESHRE Capri Workshop Group. (2003). Mono-ovulatory cycles: a key goal in profertility programmes. Human Reproduction Update, 9, 263–274.CrossRef
Fauser, B.C. and Heusden, A.M. (1997). Manipulation of human ovarian function: physiological concepts and clinical consequences. Endocrine Reviews, 18, 71–106.Google ScholarPubMed
Fauser, B.C., Devroey, P. and Macklon, N.S. (2005). Multiple birth resulting from ovarian stimulation for subfertility treatment. Lancet, 365, 1807–1816.CrossRefGoogle ScholarPubMed
Filicori, M. (1994). Gonadotrophin releasing hormone agonists. A guide to use and selection. Drugs, 48, 41–58.CrossRefGoogle Scholar
Fisher, S.A., Reid, R.L., Vught, D.A. and Casper, R.F. (2002). A randomized double blind comparison of the effects of CC and the aromatase inhitor letrozole on the ovulatory function in normal women. Fertility and Sterility, 78, 280–285.CrossRefGoogle Scholar
Glueck, C.J., Goldenberg, N., Pranikoff, J., Loftspring, M., Sieve, L. and Wang, P. (2004). Height, weight and motor-social development during the first 18 months of life in 126 infants born to 109 mothers with polycystic ovary syndrome who conceived on and continued metformin through pregnancy. Human Reproduction, 19, 1323–1330.CrossRefGoogle ScholarPubMed
Greenblatt, E. and Casper, R.F. (1987). Endocrine changes after laparoscopic ovarian cautery in polycystic ovary syndrome. American Journal of Obstetrics and Gynecology, 156, 279–285.CrossRefGoogle Scholar
Hoeger, K.M. (2006). Role of lifestyle modification in the management of polycystic ovary syndrome. Best Practice and Research in Clinical Endocrinology and Metabolism, 20, 293–310.CrossRefGoogle ScholarPubMed
Homburg, R. (2005). Clomiphene citrate-end of an era? A mini review. Human Reproduction, 20, 2043–2051.CrossRefGoogle Scholar
Hull, M.G., Glazener, C.M., Kelly, N.J., Conway, D.I., Foster, P.A., Hinton, R.A., Coulson, C., Lambert, P.A., Watt, E.M. and Desai, K.M. (1985). Population study of causes, treatment, and outcome of infertility. British Medical Journal, 291, 1693–1697.CrossRefGoogle ScholarPubMed
Hunault, C.C., Laven, J.S., Rooij, I.A., Eijkemans, M.J., te Velde, E.R. and Habbema, J.D. (2005). Prospective validation of two models predicting pregnancy leading to live birth among untreated subfertile couples. Human Reproduction, 20, 1636–1641.CrossRefGoogle ScholarPubMed
Imani, B., Eijkemans, M.J., te Velde, E.R., Habbema, J.D. and Fauser, B.C. (1998). Predictors of patients remaining anovulatory during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. Journal of Clinical Endocrinology and Metabolism, 83, 2361–2365.Google ScholarPubMed
Imani, B., Eijkemans, M.J., Faessen, G., Bouchard, P., Giudice, L.C. and Fauser, B.C. (2002a). Prediction of the individual FSH-threshold for gonadotrophin induction of ovulation in anovulatory infertility: an approach to minimize multiple gestation, ovarian hyperstimulation, and treatment expense. Fertility and Sterility, 77, 83–90.CrossRefGoogle Scholar
Imani, B., Eijkemans, M.J., te Velde, E.R., Habbema, J.D. and Fauser, B.C. (2002b). A nomogram to predict the probability of live birth after clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. Fertility and Sterility, 77, 91–97.CrossRefGoogle ScholarPubMed
Insler, V., Melmed, H., Mashiah, S., Monselise, M., Lunenfeld, B. and Rabau, E. (1968). Functional classification of patients selected for gonadotropic therapy. Obstetrics and Gynecology, 32, 620–626.Google ScholarPubMed
Kiddy, D.S., Hamilton-Fairley, D., Bush, A., Short, F., Anyaoku, V., Reed, M.J. and Franks, S. (1992). Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome. Journal of Clinical Endocrinology and Metabolism, 36, 105–111.Google ScholarPubMed
Koustra, E., White, D.M. and Franks, S. (1997). Modern use of CC in induction of ovulation. Human Reproduction Update, 3, 359–365.CrossRefGoogle Scholar
Lord, J.M., Flight, I.H.K. and Norman, R.J. (2003). Metformin in polycystic ovary syndrome: systematic review and meta-analysis. British Medical Journal, 327, 951–953.CrossRefGoogle ScholarPubMed
McGee, E.A. and Hsueh, A.J. (2000). Initial and cyclic recruitment of ovarian follicles. Endocrine Reviews, 21, 200–214.Google ScholarPubMed
Mitwally, M.F. and Casper, R.F. (2003). Aromatase inhibitors for the treatment of infertility. Expert Opinion on Investigational Drugs, 12, 353–371.CrossRefGoogle ScholarPubMed
Moll, E., Bossuyt, P.M., Korevaar, J.C., Lambalk, C.B. and Veen, F. (2006). Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial. British Medical Journal, 332, 1485.CrossRefGoogle ScholarPubMed
Mulders, A.G., Eijkemans, M.J., Imani, B. and Fauser, B.C. (2003). Prediction of chances for success or complications in gonadotrophin ovulation induction in normogonadotrophic anovulatory infertility. Reproductive Biomedicine Online, 7, 48–56.CrossRefGoogle ScholarPubMed
Nestler, J.E., Jakubowicz, D.J., Evans, W.S. and Pasquali, R. (1998). Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. New England Journal of Medicine, 338, 1876–1880.CrossRefGoogle ScholarPubMed
Norman, R.J., Davies, M.J., Lord, J. and Moran, L.J. (2002). The role of lifestyle modification in polycystic ovary syndrome. Trends in Endocrinology and Metabolism, 13, 251–257.CrossRefGoogle ScholarPubMed
Palomba, S., Orio, F., Nardo, L.G., Falbo, A., Russo, T., Corea, D., Doldo, P., Lombardi, G., Tolino, A., Colao, A. and Zullo, F. (2004). Metformin administration versus laparoscopic ovarian diathermy in clomiphene citrate-resistant women with PCOS: a prospective parallel randomized double-blind placebo-controlled trial. Journal of Clinical Endocrinology and Metabolism, 89, 4801–4809.CrossRefGoogle ScholarPubMed
PCOS consensus (2004a). The Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Human Reproduction, 19, 41–47.
PCOS consensus (2004b). The Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Fertility and Sterility, 81, 19–25.
Roozenburg, B.J., Dessel, H.J., Evers, J.L. and Bots, R.S. (1997). Successful induction of ovulation in normogonadotrophic clomiphene resistant anovulatory women by combined naltrexon and clomiphene citrate treatment. Human Reproduction, 12, 1720–1722.CrossRefGoogle ScholarPubMed
Rossing, M.A., Daling, J.R., Weiss, N.S., Moore, D.E. and Self, S.G. (1994). Ovarian tumors in a cohort of infertile women. New England Journal of Medicine, 33, 771–776.CrossRefGoogle Scholar
Roumen, F.J., Doesburg, W.H. and Rolland, R. (1984). Treatment of infertile women with a deficient postcoital test with two antiestrogens: clomiphene and tamoxifen. Fertility and Sterility, 41, 237–243.CrossRefGoogle ScholarPubMed
Rowe, P.J., Comhaire, F.H., Hargreave, T.B. and Mellows, H. (1993). WHO manual for the standardized investigation and diagnosis of the infertile couple. Cambridge University Press.Google Scholar
Rizk, B. Aboulghar (1991). Modern management of Ovarian Hyperstimulation Syndrome. Human Reproduction, 6(8), 1092–1097.Google ScholarPubMed
Rizk, B. and Smitz, J. (1992). Ovarian Hyperstimulation Syndrome after superovulation for IVF and related procedures. Human Reproduction, 7, 320–327.CrossRefGoogle ScholarPubMed
Rizk, B. (2006). Epidemiology of ovarian hyperstimulation syndrome. In Rizk, B. (Ed.) Ovarian Hyperstimulation Syndrome. Cambridge: United Kingdom, Cambridge University Press, chapter 2, 10–42.Google Scholar
Snick, H.K., Snick, T.S., Evers, J.L. and Collins, J.A. (1997). The spontaneous pregnancy prognosis in untreated subfertile couples: the Walcheren primary care study. Human Reproduction, 12, 1582–1588.CrossRefGoogle ScholarPubMed
Stafford, D.E. (2005). Altered hypothalamic-pituitary-ovarian axis function in young female athletes: implications and recommendations for management. Treatments in Endocrinology, 4, 147–154.CrossRefGoogle ScholarPubMed
Stein, I.F. and Leventhal, M.L. (1935). Amenorrhea associated with bilateral polycystic ovaries. American Journal of Gynecology, 29, 181–191.CrossRefGoogle Scholar
Tiboni, G.M. (2004). Aromatase inhibitors and teratogenesis. Fertility and Sterility, 81, 1158–1159.CrossRefGoogle ScholarPubMed
Santbrink, E.J., Hop, W.C., Dessel, H.J., Jong, F.H. and Fauser, B.C. (1995). Decremental FSH and dominant follicle development during the normal menstrual cycle. Fertility and Sterility, 64, 37–43.Google ScholarPubMed
Santbrink, E.J., Hop, W.C. and Fauser, B.C. (1997). Classification of normogonadotrophic anovulatory infertility: polycystic ovaries diagnosed by ultrasound versus endocrine characteristics of polycystic ovary syndrome. Fertility and Sterility, 67, 453–458.Google Scholar
Santbrink, E.J. and Fauser, B.C. (1997). Urinary follicle-stimulating hormone for normogonadotropic clomiphene-resistant anovulatory infertility: prospective, randomized comparison between low-dose step-up and step-down dose regimens. Journal of Clinical Endocrinology and Metabolism, 82, 3597–3602.Google ScholarPubMed
Santbrink, E.J., Hohmann, F.P., Eijkemans, M.J., Laven, S.J. and Fauser, B.C. (2005a). Does metformin modify ovarian responsiveness during exogenous FSH ovulation induction in normogonadotrophic anovulation? A placebo controlled double blind assessment. European Journal of Endocrinology, 152, 611–617.CrossRefGoogle ScholarPubMed
Santbrink, E.J., Eijkemans, M.J., Laven, S.J. and Fauser, B.C. (2005b). Patient-tailored conventional ovulation induction algorithms in anovulatory infertility. Trends in Endocrinology and Metabolism, 16, 381–389.CrossRefGoogle ScholarPubMed
Wely, M., Bayram, N., Veen, F. and Bossuyt, P.M. (2005). Predictors for treatment failure after laparoscopic electrocautery of the ovaries in women with clomiphene citrate resistant PCOS. Human Reproduction, 20, 900–905.CrossRefGoogle Scholar
White, D.M., Polson, D.W., Kiddy, D., Sagle, P., Watson, H., Gilling-Smith, C., Hamilton-Fairly, D. and Franks, S. (1996). Induction of ovulation with low-dose gonadotropins in polycystic ovary syndrome: an analysis of 109 pregnancies in 225 women. Journal of Clinical Endocrinology and Metabolism, 81, 3821–3824.Google ScholarPubMed
Yarali, H., Yildiz, B.O., Demirol, A., Zeyneloglu, H.B., Yigit, N., Bukulmez, O. and Koray, Z. (2002). Co-administration of metformin during rFSH treatment in patients with clomiphene citrate-resistant polycystic ovarian syndrome: a prospective randomized trial. Human Reproduction, 17, 289–294.CrossRefGoogle ScholarPubMed
Yen, S.S., Quigley, M.E., Reid, R.L., Ropert, J.F. and Cetel, N.S. (1985). Neuroendocrinology of opioid peptides and their role in the control of gonadotropin and prolactin secretion. American Journal of Obstetrics and Gynecology, 152, 485–493.CrossRefGoogle ScholarPubMed

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