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Reproductive Biology and Endocrinology... Aug 2023Polycystic ovarian syndrome (PCOS) is a widespread syndrome that poses unique challenges and constraints to the field of assisted reproductive technology. This condition... (Review)
Review
Polycystic ovarian syndrome (PCOS) is a widespread syndrome that poses unique challenges and constraints to the field of assisted reproductive technology. This condition is the most common cause of anovulation among infertile couples. Debate exists over the best therapeutic course of action when patients with PCOS proceed to IVF. In this review, we evaluate the best-performing and safest methods of IVF preparation, ovarian stimulation, trigger method for maturation of stimulated egg growth, and planning for embryo transfer. Pre-IVF considerations include being aware of individual AMH and vitamin D levels as well as BMI prior to selecting an ovarian stimulation protocol. Numerous supplements such as myo-inositol complement the benefits of lifestyle change and may enhance IVF performance including oocyte yield and pregnancy rate. Concerning stimulation protocols, antagonist cycles with the judicious use of GnRH agonist trigger, pre-treatment with metformin and vitamin D repletion may help mitigate the accompanied risk of ovarian hyperstimulation syndrome (OHSS). Following ovarian stimulation, PCOS patients typically undergo programmed frozen embryo transfer (FET) cycles which are more conducive for women with irregular cycles, but likely carry a higher risk of hypertensive disorders of pregnancy. However, newer stimulated FET protocols using Letrozole may offer improved outcomes. Overall, patients with PCOS require careful individual tailoring of their IVF cycle to achieve optimal results.
Topics: Pregnancy; Humans; Female; Polycystic Ovary Syndrome; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Ovarian Hyperstimulation Syndrome; Pregnancy Rate; Ovulation Induction; Infertility, Female
PubMed: 37528417
DOI: 10.1186/s12958-023-01120-7 -
Endocrinology and Metabolism (Seoul,... Apr 2021Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-aged women, characterized by hyperandrogenism, oligo/anovulation, and polycystic ovarian...
Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-aged women, characterized by hyperandrogenism, oligo/anovulation, and polycystic ovarian morphology. Combined oral contraceptives (COCs), along with lifestyle modifications, represent the first-line medical treatment for the long-term management of PCOS. Containing low doses of estrogen and different types of progestin, COCs restore menstrual cyclicity, improve hyperandrogenism, and provide additional benefits such as reducing the risk of endometrial cancer. However, potential cardiometabolic risk associated with these agents has been a concern. COCs increase the risk of venous thromboembolism (VTE), related both to the dose of estrogen and the type of progestin involved. Arterial thrombotic events related to COC use occur much less frequently, and usually not a concern for young patients. All patients diagnosed with PCOS should be carefully evaluated for cardiometabolic risk factors at baseline, before initiating a COC. Age, smoking, obesity, glucose intolerance or diabetes, hypertension, dyslipidemia, thrombophilia, and family history of VTE should be recorded. Patients should be re-assessed at consecutive visits, more closely if any baseline cardiometabolic risk factor is present. Individual risk assessment is the key in order to avoid unfavorable outcomes related to COC use in women with PCOS.
Topics: Adult; Anovulation; Contraception; Contraceptives, Oral, Combined; Female; Humans; Hyperandrogenism; Polycystic Ovary Syndrome
PubMed: 33853290
DOI: 10.3803/EnM.2021.958 -
International Journal of Gynaecology... Oct 2022Ovulatory disorders are common causes of amenorrhea, abnormal uterine bleeding, and infertility, and are frequent manifestations of polycystic ovary syndrome (PCOS)....
Ovulatory disorders are common causes of amenorrhea, abnormal uterine bleeding, and infertility, and are frequent manifestations of polycystic ovary syndrome (PCOS). There are many potential causes and contributors to ovulatory dysfunction that challenge clinicians, trainees, educators, and those who perform basic, translational, clinical, and epidemiological research. Similarly, therapeutic approaches to ovulatory dysfunction potentially involve a spectrum of lifestyle, psychological, medical, and procedural interventions. Collaborative research, effective education, and consistent clinical care remain challenged by the absence of a consensus comprehensive system for classification of these disorders. The existing and complex system, attributed to WHO, was developed more than three decades ago and did not consider more than 30 years of research into these disorders in addition to technical advances in imaging and endocrinology. This manuscript describes the development of a new classification of ovulatory disorders performed under the aegis of the International Federation of Gynecology and Obstetrics (FIGO) and conducted using a rigorously applied Delphi process. The stakeholder organizations and individuals who participated in this process comprised specialty journals, experts at large, national, specialty obstetrical and gynecological societies, and informed lay representatives. After two face-to-face meetings and five Delphi rounds, the result is a three-level multi-tiered system. The system is applied after a preliminary assessment identifies the presence of an ovulatory disorder. The primary level of the system is based on an anatomic model (Hypothalamus, Pituitary, Ovary) that is completed with a separate category for PCOS. This core component of the system is easily remembered using the acronym HyPO-P. Each anatomic category is stratified in the second layer of the system to provide granularity for investigators, clinicians, and trainees using the "GAIN-FIT-PIE" mnemonic (Genetic, Autoimmune, Iatrogenic, Neoplasm; Functional, Infectious and Inflammatory, Trauma and Vascular; Physiological, Idiopathic, Endocrine). The tertiary level allows for specific diagnostic entities. It is anticipated that, if widely adopted, this system will facilitate education, clinical care, and the design and interpretation of research in a fashion that better informs progress in this field. Integral to the deployment of this system is a periodic process of reevaluation and appropriate revision, reflecting an improved understanding of this collection of disorders.
Topics: Female; Gynecology; Humans; Polycystic Ovary Syndrome; Pregnancy; Uterine Diseases
PubMed: 35983674
DOI: 10.1002/ijgo.14331 -
Fertility and Sterility Oct 2022Ovulatory disorders are common causes of amenorrhea, abnormal uterine bleeding, and infertility, and are frequent manifestations of polycystic ovary syndrome (PCOS)....
Ovulatory disorders are common causes of amenorrhea, abnormal uterine bleeding, and infertility, and are frequent manifestations of polycystic ovary syndrome (PCOS). There are many potential causes and contributors to ovulatory dysfunction that challenge clinicians, trainees, educators, and those who perform basic, translational, clinical, and epidemiological research. Similarly, therapeutic approaches to ovulatory dysfunction potentially involve a spectrum of lifestyle, psychological, medical, and procedural interventions. Collaborative research, effective education, and consistent clinical care remain challenged by the absence of a consensus comprehensive system for classification of these disorders. The existing and complex system, attributed to WHO, was developed more than three decades ago and did not consider more than 30 years of research into these disorders in addition to technical advances in imaging and endocrinology. This manuscript describes the development of a new classification of ovulatory disorders performed under the aegis of the International Federation of Gynecology and Obstetrics (FIGO) and conducted using a rigorously applied Delphi process. The stakeholder organizations and individuals who participated in this process comprised specialty journals, experts at large, national, specialty obstetrical and gynecological societies, and informed lay representatives. After two face-to-face meetings and five Delphi rounds, the result is a three-level multi-tiered system. The system is applied after a preliminary assessment identifies the presence of an ovulatory disorder. The primary level of the system is based on an anatomic model (Hypothalamus, Pituitary, Ovary) that is completed with a separate category for PCOS. This core component of the system is easily remembered using the acronym HyPO-P. Each anatomic category is stratified in the second layer of the system to provide granularity for investigators, clinicians, and trainees using the "GAIN-FIT-PIE" mnemonic (Genetic, Autoimmune, Iatrogenic, Neoplasm; Functional, Infectious and Inflammatory, Trauma and vascular; Physiological, Idiopathic, Endocrine). The tertiary level allows for specific diagnostic entities. It is anticipated that, if widely adopted, this system will facilitate education, clinical care, and the design and interpretation of research in a fashion that better informs progress in this field. Integral to the deployment of this system is a periodic process of reevaluation and appropriate revision, reflecting an improved understanding of this collection of disorders.
Topics: Endocrinology; Female; Gynecology; Humans; Polycystic Ovary Syndrome; Pregnancy; Uterine Diseases
PubMed: 35995633
DOI: 10.1016/j.fertnstert.2022.07.009 -
Acta Medica Portuguesa Mar 2021Abnormal uterine bleeding is the most common complaint that motivates female adolescents to seek medical advice. Abnormal uterine bleeding has a significant impact on... (Review)
Review
Abnormal uterine bleeding is the most common complaint that motivates female adolescents to seek medical advice. Abnormal uterine bleeding has a significant impact on quality of life, promoting school absenteeism and limitations in social life. Moreover, episodes can vary from mild to life threatening events if not recognized and treated promptly. Healthcare providers should be able to distinguish between a normal and abnormal menstrual pattern, as this may provide early diagnosis of a potential health concern. The PALM-COEIN classification system should be used in the evaluation. Anovulation is the most frequent cause, frequently due to immaturity of the hypothalamic-pituitary-ovarian axis. A careful history and physical examination are crucial in the differential diagnosis. Management is based on both the underlying cause and the severity of bleeding. Most patients improve with pharmacological treatment, frequently requiring a multidisciplinary approach. First line treatment consists of hormonal therapy. Surgery is rarely needed. Although the prevalence of abnormal uterine bleeding is higher in adolescents compared to adults, most recommendations are not specific for this age, which makes the diagnosis and management challenging. The literature reveals lack of standardized care for adolescents and regimens vary widely. Future studies on efficacy and safety of treatments specifically in adolescents are needed.
Topics: Adolescent; Adult; Blood Coagulation Disorders; Female; Humans; Menorrhagia; Metrorrhagia; Quality of Life; Uterine Diseases; Uterine Hemorrhage
PubMed: 34214420
DOI: 10.20344/amp.12829 -
Journal of Clinical Medicine Feb 2023Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. A diagnosis of PCOS is established when a patient exhibits... (Review)
Review
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. A diagnosis of PCOS is established when a patient exhibits two of three Rotterdam criteria: oligoovulation or anovulation, excess androgen activity, and polycystic ovarian morphology. The pathogenesis of PCOS, as it affects adolescents, is often discussed in terms of a "two-hit" theory. This refers to a stepwise process in which the first "hit" is an inborn congenitally programmed predisposition, while the second "hit" arises from a provocative factor such as insulin resistance. The dynamic physiological and anatomical changes which occur in puberty make for a challenging diagnosis in this group of patients. It is important to be mindful of the physiological particularities in adolescence which often mimic the symptoms of PCOS. In their first-year post-menarche, approximately 75% of menstruating adolescents report their cycle to last between 21-45 days. Recent studies have shown that regular menstrual cyclicity is only achieved within 2-3 years post-menarche. Anovulation, as a crucial diagnostic element for PCOS, features in about half of early-post-menarchal adolescents. Hirsutism and acne are the most common clinical manifestations of hyperandrogenism, and mild features are developed by most adolescents as a result of elevated androgen levels. Distinguishing between a pathological sign and normal features of maturation is often difficult. A polycystic ovarian morphology (PCOM) through ultrasound has been found in up to 40%, 35%, and 33.3% of patients when assessed at 2, 3, and 4 years, respectively, after menarche. PCOM in adolescence is not associated with future abnormalities in ovulatory rate or menstrual cycle duration. For this reason, international guidelines recommend against the use of pelvic ultrasound until 8 years post-menarche. The primary aim of management is focused mainly on improving hormonal and metabolic status, the prevention of future comorbid complications, and generally improving the overall quality of life in young women with PCOS. Considerable controversy surrounds the choice of optimal pharmacological treatment to address PCOS in adolescents. Reliable studies, which include this sub-section of the population, are very limited. There is a lack of robust and reliable trials in the literature addressing the use of combined oral contraceptives. Further work needs to be undertaken in order to provide safe and effective care to the adolescent population in this regard.
PubMed: 36769869
DOI: 10.3390/jcm12031221 -
Molecular Metabolism May 2020Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among reproductive age women. Although its cardinal manifestations include hyperandrogenism,...
BACKGROUND
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among reproductive age women. Although its cardinal manifestations include hyperandrogenism, oligo/anovulation, and/or polycystic ovarian morphology, PCOS women often display also notable metabolic comorbidities. An array of pathogenic mechanisms have been implicated in the etiology of this heterogeneous endocrine disorder; hyperandrogenism at various developmental periods is proposed as a major driver of the metabolic and reproductive perturbations associated with PCOS. However, the current understanding of the pathophysiology of PCOS-associated metabolic disease is incomplete, and therapeutic strategies used to manage this syndrome's metabolic complications remain limited.
SCOPE OF REVIEW
This study is a systematic review of the potential etiopathogenic mechanisms of metabolic dysfunction frequently associated with PCOS, with special emphasis on the metabolic impact of androgen excess on different metabolic tissues and the brain. We also briefly summarize the therapeutic approaches currently available to manage metabolic perturbations linked to PCOS, highlighting current weaknesses and future directions.
MAJOR CONCLUSIONS
Androgen excess plays a prominent role in the development of metabolic disturbances associated with PCOS, with a discernible impact on key peripheral metabolic tissues, including the adipose, liver, pancreas, and muscle, and very prominently the brain, contributing to the constellation of metabolic complications of PCOS, from obesity to insulin resistance. However, the current understanding of the pathogenic roles of hyperandrogenism in metabolic dysfunction of PCOS and the underlying mechanisms remain largely incomplete. In addition, the development of more efficient, even personalized therapeutic strategies for the metabolic management of PCOS patients persists as an unmet need that will certainly benefit from a better comprehension of the molecular basis of this heterogeneous syndrome.
Topics: Adipose Tissue; Androgens; Animals; Bariatric Surgery; Female; Humans; Hyperandrogenism; Insulin Resistance; Metabolic Syndrome; Mice; Obesity; Polycystic Ovary Syndrome
PubMed: 32244180
DOI: 10.1016/j.molmet.2020.01.001 -
Journal of Assisted Reproduction and... Mar 2022Polycystic ovary syndrome (PCOS) is a major cause of female infertility, being present in up to 20% of women of childbearing age. Insulin resistance (IR) plays an... (Review)
Review
PURPOSES
Polycystic ovary syndrome (PCOS) is a major cause of female infertility, being present in up to 20% of women of childbearing age. Insulin resistance (IR) plays an important role in the pathophysiology of PCOS; therefore, its treatment may benefit women with the syndrome. The main drug used for IR management is metformin (MT). We aim to review the literature on the use of metformin in women with PCOS.
METHODS
Using the terms "metformin" and "polycystic ovary syndrome," we conducted a search the PubMed, EMBASE, and Google Scholar databases. The research was restricted to articles published in English. Initially, only published meta-analyses were included, in the absence of meta-analyzes, RCT and well-designed prospective studies were used.
RESULTS
Metformin increases success rates and decreases complication rates when used as an adjunctive medication for ovulation induction during low complexity assisted reproduction treatments and during ovarian stimulation for in vitro fertilization in women with PCOS. Evidence about the effect of metformin on fetal and obstetric complication rates is conflicting. Metformin is associated with high incidence of gastrointestinal symptoms; however, serious adverse effects are rare and there is no evidence of teratogenicity.
CONCLUSION
For women with PCOS, metformin is a good adjunctive medication for ovulation induction/stimulation for high and low complexity assisted reproduction therapies. The adverse effects are mostly mild, and there is no risk of teratogenicity, but the risk of long-term complications for the offspring is not yet defined. High heterogeneity of the studies limits extrapolation of findings, and further research is needed to determine which women will benefit most from the medication.
Topics: Clomiphene; Female; Fertility Agents, Female; Humans; Hypoglycemic Agents; Infertility, Female; Insulin Resistance; Live Birth; Metformin; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Prospective Studies
PubMed: 35156149
DOI: 10.1007/s10815-022-02429-9 -
Reproductive Biology and Endocrinology... Jun 2023Over the past decade, the application of frozen-thawed embryo transfer treatment cycles has increased substantially. Hormone replacement therapy and the natural cycle... (Review)
Review
Over the past decade, the application of frozen-thawed embryo transfer treatment cycles has increased substantially. Hormone replacement therapy and the natural cycle are two popular methods for preparing the endometrium. Hormone replacement therapy is now used at the discretion of the doctors because it is easy to coordinate the timing of embryo thawing and transfer with the schedules of the in-vitro fertilization lab, the treating doctors, and the patient. However, current results suggest that establishing a pregnancy in the absence of a corpus luteum as a result of anovulation may pose significant maternal and fetal risks. Therefore, a 'back to nature' approach that advocates an expanded use of natural cycle FET in ovulatory women has been suggested. Currently, there is increasing interest in how the method of endometrial preparation may influence frozen embryo transfer outcomes specifically, especially when it comes to details such as different types of ovulation monitoring and different luteal support in natural cycles, and the ideal exogenous hormone administration route as well as the endocrine monitoring in hormone replacement cycles. In addition to improving implantation rates and ensuring the safety of the fetus, addressing these points will allow for individualized endometrial preparation, also as few cycles as possible would be canceled.
Topics: Pregnancy; Female; Humans; Pregnancy Rate; Cryopreservation; Embryo Transfer; Endometrium; Hormones; Retrospective Studies
PubMed: 37291605
DOI: 10.1186/s12958-023-01106-5