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Cambridge University Press
Online publication date:
August 2011
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Book description

Ovarian Stimulation covers all the basic and advanced aspects of ovarian stimulation for women undergoing ovulation induction and assisted reproduction. It gives a comprehensive review of the modern approach to ovarian stimulation and its alternatives - both in IVF and in other areas of reproductive endocrinology where it is employed. The book is divided into six sections that cover mild forms, non-conventional forms, IVF, complications and their management, alternatives, and procedures. The chapters are clearly written and well illustrated, discussing a wide range of relevant topics, including the protocols of gonadotropin, oral agents for ovulation induction, aromatase inhibitors and surgical induction of ovulation, ovarian hyperstimulation syndrome, and alternatives to drug treatment. Written by leading experts on reproductive health and fertility, it will assist infertility specialists, gynecologists, reproductive endocrinologists and radiologists in determining their patients' treatment.

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Page 1 of 2

  • Chapter 7 - Gonadotropins in ovarian stimulation
    pp 61-66
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    This chapter reviews pharmacological agents with a focus on the clinical aspects of their use. There are two groups of pharmacological agents for ovarian stimulation: the first group includes injectable gonadotropins and the second group includes oral agents that are estrogen modulators. Enclomiphene is the more potent antiestrogenic isomer and the one primarily responsible for the ovulation-stimulation actions of clomiphene citrate (CC). It is important to stress the two main prerequisites for the success of CC ovarian stimulation: presence of reasonable estrogen levels in the body and an intact hypothalamic/pituitary axis capable of producing endogenous gonadotropins. Aromatase activity is present in many normal tissues, such as the ovaries, the brain, muscle, liver, breast tissue, as well as in pathological tissues such as malignant breast tumors. The short half-life of letrozole and absence of estrogen receptor antagonism result in a very favorable profile for infertility treatment compared with CC.
  • Chapter 9 - Ovarian hyperstimulation for poor responders
    pp 77-86
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    Clinical manifestation of anovulation is oligomenorrhea or amenorrhea. Patients with hyperandrogenemia and polycystic ovaries (without ovulation disorders) and patients with polycystic ovaries and ovulation disorders (without hyperandrogenism) may now be included in polycystic ovary syndrome (PCOS) diagnosis. The majority of anovulatory patients (about 80%) will have normal serum concentrations of estradiol (E2) and follicle-stimulating hormone (FSH) and a small proportion (approximately 10%) decreased concentrations of both hormones. Traditionally, ovulation induction treatment in normogonadotropic anovulation is started with an antiestrogen (CC) and, in case of treatment failure or absence of conception, this is followed by exogenous FSH. The most serious complications resulting from ovulation induction are caused by the limited control of follicular development. Increased availability of genetic profiles will be helpful to accomplish a more patient-tailored approach by identification of beneficial subgroups for certain interventions.
  • Chapter 10 - Polycystic ovarian syndrome
    pp 87-102
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    This chapter focuses on the indications for intrauterine insemination (IUI) in combination with mild ovarian hyperstimulation (MOH), its methods and risks. Optimal timing of the insemination is a crucial factor in IUI programs. After ovulation oocytes should be fertilized within several hours. Inseminated sperm (bypassing the cervix which acts as a reservoir for spermatozoa) has a limited period of survival, and sperm should therefore not be inseminated too early. When MOH is applied in IUI programs, one should strive after multifollicular growth of two to three dominant follicles to obtain the highest probability of conception with reasonable risks. When multiple pregnancies are kept to a minimum, MOH/IUI is more cost-effective compared with in vitro fertilization (IVF). Gonadotropins are the most effective drugs and should be offered in a low-dose, step-up protocol. Future randomized trials should investigate the cost-effectiveness of luteal support.
  • Chapter 11 - Ovarian hyperstimulation syndrome
    pp 103-129
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    This chapter explores the concerns with conventional ovarian stimulation regimens, which have provoked a need to develop alternative strategies. Natural and modified natural cycles for in vitro fertilization (IVF) are briefly discussed. Elective single embryo transfer correlates well with the NHS funding policy. However, as long as couples pay for IVF treatments themselves, many of them will opt for double embryo transfer because it can result in a higher chance of success in older women. Clomiphene citrate (CC) acts antagonistically on the estradiol receptor at the hypothalamic level, inhibiting negative as well as positive feedback, and resulting in ovarian stimulation and suppression of the luteinizing hormone (LH) surge. To improve effectiveness, natural cycle IVF could be offered as a series of treatment cycles, since it is safer and less stressful compared with conventional stimulation. Mild ovarian stimulation aims at reducing the psychological burden of IVF treatment.
  • Chapter12 - How to select ovarian stimulation protocols to avoid difficulties and complications
    pp 130-142
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    The aim of treatment with a gonadotropin-releasing hormone (GnRH) agonist is elimination of the luteinizing hormone (LH) surge and fluctuating LH concentrations, which compromise outcome in cycles of ovarian stimulation for in-vitro fertilization (IVF). This chapter addresses the characteristics of the standard long-course protocol. It is most common to initiate treatment in the luteal phase to minimize the consequences of the flare effect seen in the first few days of treatment with a GnRH agonist. The down-regulation effect of agonists can be established and maintained by multiple applications of nasal spray, single daily injection, or depo formulations lasting variable lengths of time. When the patient is down-regulated at the start of follicle stimulating hormone (FSH) treatment, subsequent follicular growth and recruitment is dictated by two elements: the ovarian reserve, which dictates the number of follicles available for recruitment, and the profile of circulating FSH concentrations.
  • Chapter 14 - Chorionic gonadotropin and luteinizing hormone supplementation during ovarian stimulation
    pp 151-161
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    This chapter reviews the role of gonadotropin-releasing hormone (GnRH) antagonists in ovulation induction for in vitro fertilization (IVF). Although the purpose of the development of GnRH antagonists was originally a non-steroid contraceptive drug, it was found that GnRH antagonists have potential benefit in assisted reproduction. GnRH antagonists act by immediate suppression of pituitary gonadotropin release and rapid recovery of normal secretion of endogenous luteinizing hormone (LH) and follicle stimulating hormone (FSH). The inhibition of LH secretion is more pronounced than that of FSH, this being most likely due to the different forms of gonadotropin regulation and the prolonged FSH half-life, or the immunoactive and bioactive forms of FSH. The effect of oral contraceptive pills (OCP) for cycle scheduling prior to GnRH antagonist protocol on IVF cycle parameters and pregnancy outcome was studied. All OCP-pretreated cycles required significantly longer stimulation than non-pretreated cycles and higher total dosage of FSH.
  • Chapter 15 - Ovulation induction for hypogonadotropic hypogonadism
    pp 162-172
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    This chapter deals with different gonadotropin molecules in ovarian stimulation. Human menopausal gonadotropins consist of a purified preparation of gonadotropins extracted from the urine of postmenopausal women. In the natural cycle both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are required for normal follicular growth and maturation. The main risk associated with the use of FSH-containing gonadotropin products is the development of ovarian hyperstimulation syndrome (OHSS). OHSS can be easily prevented by starting with a relatively low dose of gonadotropin, especially in high-risk women like young patients, those with polycystic ovary syndrome (PCOS), and those with a low body mass index (BMI). From the many randomized trials that have been performed it appears that all available gonadotropins are comparably effective and safe. The differences in isoform profile did not appear to have significant clinically significant effects in in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles.
  • Chapter16 - Natural cycle IVF
    pp 173-180
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    Controlled ovarian stimulation (COS) for in vitro fertilization-embryo transfer (IVF-ET) induces dramatic changes in the hormonal profile of the menstrual cycle. When participants were analyzed according to the gonadatrophin-releasing hormone (GnRH) analogue used for pituitary down-regulation, significantly higher serum progesterone (P) levels were observed with GnRH agonists versus antagonists. Patients with lower P levels demonstrated significantly better ongoing pregnancy rates compared with those showing higher levels of P, and this remained the case when pregnancy rates were corrected for confounding factors, including female age and body mass index (BMI). It is been suggested that serum accumulation of human chorionic gonadotropin (hCG) arising from human menopausal gonadotropin (hMG) could be responsible for elevated P levels. The high serum P levels on the day of hCG administration are a frequent event in GnRH agonist and antagonist IVF/intracytoplasmic sperm injection (ICSI) -ET cycles and is associated with a decreased pregnancy rate.

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