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Ovarian stimulation aims at the development of one or more of the ovarian follicles to reach the stage of maturity culminating in the release of one or more mature oocytes ready for fertilization. Ovarian follicular development is under the control of local factors inside the ovaries (most of it is poorly understood), as well as hormones produced from extraovarian sources, mainly pituitary gonadotropins. Other hormones may play a role in ovarian follicular development; the extent and details of such a role are not fully understood.
Since first reports in the literatures by Mitwally and Casper, along the last two decades, the aromatase inhibitor letrozole has been found as a useful and safe agent for ovulation induction in anovulatory women, e.g., PCOS (Polycystic Ovarian Syndrome), ovarian superovulation in ovulatory women, e.g., unexplained infertility, and in conjunction with gonadotropins to achieve better ovarian response during assisted reproduction (1-5). This debate discusses if ultrasound is ‘not’ required during letrozole treatment ‘alone’ as an agent for ovarian stimulation. I am against not using ultrasound monitoring during letrozole treatment. I think ultrasound is required in patients undergoing letrozole treatment, at two points: a baseline ultrasound when starting administration and a follow-up ultrasound few days after finishing letrozole administration. Ultrasound during letrozole treatment may be highly recommended, advisable and least required in the following situations: Highly recommended for safety when ruling out possible underlying pregnancy and ovarian cysts; Advisable to determine stimulation protocol, and response to letrozole treatment, as well as timing HCG administration and fertility treatment including timing intercourse and IUI; Least required to determine the risk of multiple pregnancy which is pretty low with letrozole treatment.
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.
Three-dimensional (3D) ultrasound technologies are beneficial in some applications of obstetrics and gynecology and may aid in the evaluation of abnormal ovaries. Although the diagnostic criteria of polycystic ovary syndrome (PCOS) do not include 3D imaging, Allemand performed a study establishing the diagnostic threshold for 3D Ultrasonography of PCOS. The administration of gonadotropins for both insemination cycles as well as in-vitro fertilization cycles relies upon the use of serial real-time ultrasound examinations. In clinical practice, TV ultrasound monitoring during controlled ovarian hyperstimulation (COH) is performed to improve safety and precise monitoring of ovarian response to gonadotropin stimulation. PCOS patients have an increased number of preantral follicles; hence, close monitoring for ovarian hyperstimulation syndrome (OHSS) is essential. 3D ultrasound is a new imaging modality that improves the sensitivity and specificity of ultrasound. Recent advances in 3D ultrasound have the potential to better our understanding of follicular development, ovulation, and uterine receptivity.
This chapter presents a comprehensive review of the reproductive problems that could be associated with uterine septum. The classification of uterine anomalies divides the uterine septum into complete (septate) or partial (subseptate) groups, according to whether the septum approaches the internal os or not, respectively. Although surgery (hysteroscopy, alone or with laparoscopy) constitutes the gold standard for the diagnosis of uterine septum, various imaging tools including hysterosalpingography (HSG), ultrasonography, and magnetic resonance imaging (MRI) have great value in the diagnosis with high level of accuracy. The hysteroscopic approach for surgical resection of uterine septum is a safe and effective approach. While generally it is an operator preference whether to utilize ablative energy, for example, electrical diathermy or laser, or to utilize sharp scissors without energy, the outcome of treatment is comparable as regards complication and reproductive performance after surgery.
This chapter discusses the potential role of the new group of medications called aromatase inhibitors in assisted reproduction. When an aromatase inhibitor is applied during controlled ovarian hyperstimulation (COO), estrogen production per growing ovarian follicle has been found to be significantly lower than when aromatase inhibitors are not used. The use of aromatase inhibitors for in vitro maturation is an exciting application that can involve a brief aromatase inhibitor-induced rise in endogenous gonadotropin secretion leading to multiple ovarian follicles, followed by retrieval of immature oocytes. Both lowering supraphysiological levels of estrogen during COH and improving response to COH by enhancing endogenous gonadotropin production and increasing the ovarian follicular sensitivity to gonadotropin stimulation could be of benefit in particular groups of patients, for example, poor responders, endometriosis-associated infertility, polycystic ovarian syndrome (PCOS), and survivors of estrogen-dependant malignancies, for example, breast cancer.
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