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13 results

  • Does Pten have an impact on oogenesis of PCOS mouse models?

  • T. Onal, P. Tulay, H.S. Vatansever
  • Journal:
    Zygote / Volume 31 / Issue 1 / February 2023
    Published online by Cambridge University Press:
    19 December 2022, pp. 97-100
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  • Polycystic ovary syndrome (PCOS) is a complex disorder in which the aetiology is still not explained very well. The PI3K/PTEN (phosphatidylinositol 3-kinase/phosphatase and tensin homolog deleted on chromosome 10) pathway is an important pathway that is involved in many mechanisms, including proliferation, growth and motility. PTEN plays a role in granulosa cell proliferation and regulates the differentiation process. The aim of this study was to investigate the expression levels of Pten and Pik3ca in PCOS mouse models with and without any treatment procedures. Three groups of mouse models, PCOS, a PCOS group with clomiphene citrate treatment, and a PCOS group with the combination of clomiphene citrate, metformin and pioglitazone treatment, were established. Ovarian tissues, which were obtained from these groups and a control group with no PCOS, were embedded in paraffin and RNA was extracted. cDNA was synthesized and real-time PCR was conducted to evaluate the expression levels of Pten and Pik3ca. The results of this study showed that both Pten and Pik3ca genes were expressed in the ovarian tissues from the mouse models. Although one-way analysis of variance results showed that Pten was expressed significantly differently in the samples, individual Student’s t-tests did not show any significantly different expression levels in each group. This study is important as it shows the expression patterns of two genes in PCOS mouse models with different treatment strategies, including clomiphene citrate, metformin and pioglitazone. The results of this study formed the basis of research studies and investigations into different genes within the PTEN pathway, as well as other pathways that are under investigation.

  • Chapter 7 - “It’s Complicated”: The Intersect Between Psychiatric Disorders and Infertility

  • from II - Therapeutic Approaches
  • Edited by Sharon N. Covington
  • Book:
    Fertility Counseling: Clinical Guide
    Published online:
    24 November 2022
    Print publication:
    08 December 2022, pp 79-87

  • Summary

    The experience of Infertility is extremely stressful for all people.The goals of this chapter are to provide the mental health practitioner with an understanding of the relationship between infertility in men and women and psychiatric illnesses. Patients with a history of major depression are at an increased risk of recurrence of major depression during infertility evaluation and treatment, and women who have had recurrent miscarriages are especially high risk for depression. Some patients will need to continue their antidepressants during the infertility process and pregnancy, and in this chapter we will discuss the risks and benefits associated with antidepressants in this population. Research on the interaction of the infertility medications and bipolar disorder destabilization is lacking, but it is important for the mental health practitioner to recognize that the dramatic hormonal changes associated with ovarian stimulation may lead to increased lability, especially if the medications have the side effect of insomnia. While some mood stabilizers such as lamotrigine are considered relatively safe to take in pregnancy, others, such as valproic acid are associated with congenital abnormalities and should be discontinued. Personality disorder patients may also react to the stress of infertility treatment with primitive defenses that are difficult for the infertility treatment team to manage, such as acting out and splitting. In this chapter, we will discuss the intersection of personality disorders and psychiatry and we will also provide guidance about when to recommend that patients defer or stop infertility treatment due to psychiatric illnesses.

  • Chapter 11 - Ovulation Induction in Polycystic Ovary Syndrome

  • Edited by Gabor T. Kovacs, Bart Fauser, Richard S. Legro
  • Book:
    Polycystic Ovary Syndrome
    Published online:
    13 May 2022
    Print publication:
    02 June 2022, pp 102-109

  • Summary

    Chronic anovulation is a very common disorder in polycystic ovary syndrome (PCOS) patients wishing to conceive. In these patients, ovulation induction resulting in restoration of a regular menstrual cycle with monofollicular ovulation may normalize the probability of pregnancy. This may be achieved either by increasing the follicle-stimulating hormone (FSH) serum concentration or by improving the endocrine ovarian milieu resulting in enhanced FSH responsiveness of the ovaries. Later on, this favorable endocrine milieu may also benefit implantation, embryo development and reduce risks in pregnancy for mother and child. A combination of both strategies could be used to individualize treatment in a patient-tailored way: for every patient an optimal effective treatment plan based on specific individual characteristics. Although there has been a tendency to ultimately skip ovulation induction and start in vitro fertilization (IVF) immediately because this would result in better pregnancy chances, this choice neglects the significant risks and physical burden of IVF treatment and significant higher costs. Ovulation induction in PCOS patients, as discussed in this chapter, is a very successful treatment option with a cumulative single live birth of greater than 70% during a 24-month follow-up period.

  • Chapter 19 - Granulosa cells and their impact on human ART

  • Edited by David K. Gardner, University of Melbourne, Botros R. M. B. Rizk, University of South Alabama, Tommaso Falcone
  • Book:
    Human Assisted Reproductive Technology
    Published online:
    16 May 2011
    Print publication:
    31 March 2011, pp 209-222

  • Summary

    The majority of women with anovulation or oligoovulation due to polycystic ovary syndrome (PCOS) often have clinical and/or biochemical evidence of hyperandrogenism. This chapter describes the treatment with clomiphene citrate (CC), aromatase inhibitors (AIs), gonadotropins, and metformin followed by a discussion on the management of women with PCOS undergoing in vitro fertilization (IVF). It deals with the combined treatment of clomiphene with metformin. In women with PCOS, metformin is said to lower fasting insulin concentrations but also probably acts directly on theca cells and attenuates androgen production. The aim of the chronic low-dose step-up protocol is to obtain the ovulation of a single follicle. While results of IVF for women with PCOS are generally satisfactory compared with those with normal ovaries, ovarian stimulation protocols must be adapted accordingly to avoid the major pitfall of ovarian hyperstimulation syndrome (OHSS) in these women.

  • Chapter 17 - In vitro maturation of oocytes

  • from Section 5: - Alternatives to ovarian hyperstimulation
  • Edited by Mohamed Aboulghar, Botros Rizk, University of South Alabama
  • Book:
    Ovarian Stimulation
    Published online:
    05 August 2011
    Print publication:
    23 December 2010, pp 181-194

  • Summary

    Management of the poor responder remains one of the greatest challenges of controlled ovarian hyperstimulation (COH) in preparation for the assisted reproductive technologies. This chapter reviews a variety of approaches which have been employed in this poorly defined patient group. The profound suppression of gonadotropins induced by traditional long luteal gonadotropin-releasing hormone agonist (GnRHa) protocols may be particularly devastating for poor responders. Decreasing the GnRHa dose during the luteal phase prior to COH would theoretically decrease the extent of endogenous gonadotropin suppression while preventing premature ovulation. The administration of estradiol in the luteal phase may induce follicle-stimulating hormone (FSH) receptor formation in more resistant follicles and result in a more coordinated gonadotropin response. The ability to enhance endogenous follicular phase gonadotropin release by the administration of either clomiphene citrate or an aromatase inhibitor would represent an attractive adjunct to GnRHant protocols in poor-responder patients.

  • Chapter 7 - Gonadotropins in ovarian stimulation

  • from Section 2: - Ovarian hyperstimulation for IVF
  • Edited by Mohamed Aboulghar, Botros Rizk, University of South Alabama
  • Book:
    Ovarian Stimulation
    Published online:
    05 August 2011
    Print publication:
    23 December 2010, pp 61-66

  • Summary

    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 11 - Ovarian hyperstimulation syndrome

  • from Section 3: - Difficulties and complication of ovarian stimulation
  • Edited by Mohamed Aboulghar, Botros Rizk, University of South Alabama
  • Book:
    Ovarian Stimulation
    Published online:
    05 August 2011
    Print publication:
    23 December 2010, pp 103-129

  • Summary

    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.

  • Chapter 20 - Scrotal ultrasonography in male infertility

  • from Section 2: - Ultrasonography in infertility
  • Edited by Botros R. M. B. Rizk, University of South Alabama
  • Book:
    Ultrasonography in Reproductive Medicine and Infertility
    Published online:
    07 September 2011
    Print publication:
    25 March 2010, pp 163-170

  • Summary

    When clomiphene citrate (CC) is used for ovulation induction, endometrial thickness is often decreased compared with spontaneous cycles during and immediately following the days CC is taken, because of its antiestrogen effect. A triple-line pattern on the day of human chorionic gonadotropin (hCG) administration has been reported to be necessary for implantation in controlled ovarian hyperstimulation (COH) cycles, where human menopausal gonadotropin (hMG) or follicle stimulating hormone (FSH) is administered. A triple-line endometrial pattern on the day of hCG administration in in-vitro fertilization (IVF) cycles is related to serum estradiol level, the number of mature oocytes, and the number of top-quality embryos and is unrelated to serum progesterone levels. Preclinical miscarriage, also referred to as biochemical pregnancy, in which quantitative hCG levels initially indicate pregnancy but decrease before a gestational sac can be seen on ultrasound, and clinical miscarriage of embryos with karyotype is the result of inadequate endometrial development.

  • 32 - Endometriosis-Associated Infertility

  • from PART II - INFERTILITY EVALUATION AND TREATMENT
  • Edited by Botros R. M. B. Rizk, University of South Alabama, Juan A. Garcia-Velasco, Hassan N. Sallam, Antonis Makrigiannakis, University of Crete
  • Book:
    Infertility and Assisted Reproduction
    Published online:
    04 August 2010
    Print publication:
    15 September 2008, pp 302-308

  • Summary

    This chapter illustrates the different opinions regarding the pathophysiology and management of endometriosis-associated infertility. Pelvic inflammation due to endometriosis may cause adhesion formation and scarring, which leads to a disruption and decrease in fertility. Medical treatment using GnRH agonists can only be used prior to in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). When moderate or severe endometriosis causes anatomic distortion of the pelvis in women who wish to maintain or restore fertility, surgery may be the treatment of choice. Clomiphene citrate and intrauterine insemination (IUI) treatment triple the monthly fecundity rate from 3.3 to 9.5 percent, as compared with nontreatment cycles, in patients with surgically corrected endometriosis. If laparoscopic surgery will be performed before IVF-ICSI cycles, a less invasive and conservative technique should be used during the operation such as cyst aspiration or fenestration.

  • 30 - Medical Management of Polycystic Ovary Syndrome

  • from PART II - INFERTILITY EVALUATION AND TREATMENT
  • Edited by Botros R. M. B. Rizk, University of South Alabama, Juan A. Garcia-Velasco, Hassan N. Sallam, Antonis Makrigiannakis, University of Crete
  • Book:
    Infertility and Assisted Reproduction
    Published online:
    04 August 2010
    Print publication:
    15 September 2008, pp 286-293

  • Summary

    This chapter discusses polycystic ovary syndrome (PCOS) and its clinical manifestations. It also explores the incidence of insulin resistance in PCOS. Insulin resistance can be encountered in women with PCOS. Diagnosis and treatment are also independent on insulin resistance. Management of women with PCOS depends on the symptoms. These could be ovulatory dysfunction-related infertility, menstrual disorders, or hirsutism. Treatment of hirsutism involves administration of oral contraceptive pills and antiandrogens. Clomiphene citrate, dexamethazone, gonadotropin and aromatase inhibitors are used in the treatment of ovulatory disorders. Gonadotropin-releasing hormone agonist plays a major role in IVF treatment as well as in superovulation. There are several insulin-sensitizing agents available to reduce insulin levels, and the most commonly used for women with PCOS is metformin. Metformin has replaced the surgical treatment of PCOS with ovarian drilling. Metformin improves insulin resistance and hyperandrogenism, decreases serum lipids, and improves glucose homeostasis.

  • 31 - Surgical Management of Polycystic Ovary Syndrome

  • from PART II - INFERTILITY EVALUATION AND TREATMENT
  • Edited by Botros R. M. B. Rizk, University of South Alabama, Juan A. Garcia-Velasco, Hassan N. Sallam, Antonis Makrigiannakis, University of Crete
  • Book:
    Infertility and Assisted Reproduction
    Published online:
    04 August 2010
    Print publication:
    15 September 2008, pp 294-301

  • Summary

    This chapter focuses on the surgical management of polycystic ovary syndrome (PCOS). The mechanism of action of laparoscopic ovarian drilling (LOD) is unclear. Its beneficial effect is apparently due to destruction of the androgen-producing stroma. Patients who were resistant to clomiphene citrate (CC) may respond to this medication after the procedure. Sensitivity to exogenous gonadotrophin treatment is increased. Gonadotrophin treatment following LOD is associated with a lower duration of stimulation, lower total dose of gonadotrophins, and higher pregnancy rates. LOD and metformin therapy improve menstrual disturbances and ovulatory dysfunction to a similar extent. The pregnancy rates after both treatments are also similar, but the safety of metformin in pregnancy is unproven. The improvement in hyperandrogenism is thought to be secondary to the reduction in LH concentrations and the decreased androgen production by the ovarian stroma.

  • 28 - Reducing the Risk of High-Order Multiple Pregnancy Due to Ovulation Induction

  • from PART II - INFERTILITY EVALUATION AND TREATMENT
  • Edited by Botros R. M. B. Rizk, University of South Alabama, Juan A. Garcia-Velasco, Hassan N. Sallam, Antonis Makrigiannakis, University of Crete
  • Book:
    Infertility and Assisted Reproduction
    Published online:
    04 August 2010
    Print publication:
    15 September 2008, pp 258-269

  • Summary

    Ovulation induction (OI) that is not part of an in vitro fertilization (IVF) cycle is the cause of 40-70 percent of high-order multiple pregnancies (HOMP), pregnancies with three or more conceptus, and 11-21 percent of twins, in countries where modern infertility treatment is practiced. Clomiphene Citrate (CC) increases follicular stimulation hormone (FSH) secretion from the pituitary by temporarily blocking the negative feedback of estrogen that is necessary to regulate production and secretion of FSH. Pulsatile gonadotropin-releasing hormone (GnRH) administered subcutaneously or intravenously results in pregnancy and multiple pregnancies similar to low-dose gonadotropins. A widely used technique for reducing HOMP during controlled ovarian hyperstimulation-intauterine insemination (COH-IUI) treatment is to withhold human chorionic gonadotropin (hCG) administration when excessive numbers of follicles or estradiol (E) concentrations are present. OI should not be attempted, and IVF should be used instead for women who cannot safely carry a twin pregnancy.

  • 5 - Treatment options prior to IVF

    • By Roger Hart, UWA School of Women's and Infant's Health, Subiaco, Australia, Melanie Davies, Reproductive Medicine Unit, Elizabeth Garrett Anderson Hospital and Obstetric Hospital, London, UK
  • Edited by Paul Serhal, Caroline Overton
  • Book:
    Good Clinical Practice in Assisted Reproduction
    Published online:
    22 October 2009
    Print publication:
    01 July 2004, pp 100-111

  • Summary

    The treatment options that face a couple prior to in vitro fertilisation (IVF) depend upon the cause of their infertility. To clarify the definition of male factor subfertility to produce a pragmatic approach to treatment, Van Voorhis published a study that correlates the effect of the total motile sperm count with the outcome of assisted reproduction. A diagnosis of unexplained infertility cannot be made without a laparoscopy to exclude the presence of pelvic adhesions or endometriosis. There is evidence that in couples with otherwise unexplained infertility, the fecundity of women with minimal and mild endometriosis is improved by laparoscopic ablation of the endometriotic deposits. The commonest cause of anovulatory infertility is polycystic ovarian syndrome (PCOS). Unexplained infertility is reported to occur in up to 60% of couples. The simplest, least invasive and cheapest regime for superovulation and intrauterine insemination (IUI) is the use of clomiphene citrate.