PCOS (Polycystic ovary syndrome), a hormonal disorder causing enlarged ovaries with small cysts, or fluid-filled sacs. It is a condition in which a woman's hormones are out of balance. It's a health problem that affects 1 in 10 women of childbearing age. Over the years, numerous hypothesis have been proposed regarding the proximate physiological origin for PCOS. Difference between PCOD & PCOS is important to know. A common confusion among women, is understanding the difference between having PCOS & having been diagnosed with it.
Various researches have studied the prevalence of PCOS in India (Tamil Nadu, Mumbai, Karnataka & Lucknow). Maintaining a good health is essential to prevent as well as treat hormonal disturbances & conditions. Management of these both at risk for PCOS and those with a confirmed PCOS diagnosis includes education, healthy lifestyle and therapeutic interventions targeting their symptoms.
Polycystic ovarian syndrome (PCOS) is a condition
of unexplained hyperandrogenic chronic anovulation
that most likely represents a heterogenous disorder.
About 10% of women in the reproductive age group
suffer from this disorder.
PCOS (Polycystic ovary syndrome), a hormonal disorder causing enlarged ovaries with small cysts, or fluid-filled sacs. It is a condition in which a woman's hormones are out of balance. It's a health problem that affects 1 in 10 women of childbearing age. Over the years, numerous hypothesis have been proposed regarding the proximate physiological origin for PCOS. Difference between PCOD & PCOS is important to know. A common confusion among women, is understanding the difference between having PCOS & having been diagnosed with it.
Various researches have studied the prevalence of PCOS in India (Tamil Nadu, Mumbai, Karnataka & Lucknow). Maintaining a good health is essential to prevent as well as treat hormonal disturbances & conditions. Management of these both at risk for PCOS and those with a confirmed PCOS diagnosis includes education, healthy lifestyle and therapeutic interventions targeting their symptoms.
Polycystic ovarian syndrome (PCOS) is a condition
of unexplained hyperandrogenic chronic anovulation
that most likely represents a heterogenous disorder.
About 10% of women in the reproductive age group
suffer from this disorder.
Pcos by dr alka mukherjee dr apurva mukherjee nagpur m.s.alka mukherjee
Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine-metabolic disorder that implies various severe consequences to female health, including alarming rates of infertility. Although its exact etiology remains elusive, it is known to feature several hormonal disturbances, including hyperandrogenemia, insulin resistance (IR), and hyperinsulinemia. Insulin appears to disrupt all components of the hypothalamus-hypophysis-ovary axis, and ovarian tissue insulin resistance results in impaired metabolic signaling but intact mitogenic and steroidogenic activity, favoring hyperandrogenemia, which appears to be the main culprit of the clinical picture in PCOS. In turn, androgens may lead back to IR by increasing levels of free fatty acids and modifying muscle tissue composition and functionality, perpetuating this IR-hyperinsulinemia-hyperandrogenemia cycle. Nonobese women with PCOS showcase several differential features, with unique biochemical and hormonal profiles. Nevertheless, lean and obese patients have chronic inflammation mediating the long term cardiometabolic complications and comorbidities observed in women with PCOS, including dyslipidemia, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Given these severe implications, it is important to thoroughly understand the pathophysiologic interconnections underlying PCOS, in order to provide superior therapeutic strategies and warrant improved quality of life to women with this syndrome.
Polycystic Ovarian Syndrome is heterogeneous, multisystem endocrinopathy in women of reproductive age characterized by chronic anovulation resulting in infertility, irregular bleeding, obesity and hirsutism. Most common, although the least understood, cause of androgen excess. Initially it was described in 1935.Also known as Stein-Leventhal syndrome
The slide includes:
Introduction
Incidence
Pathophysiology
Pathology
Clinical features
Investigation
Treatment
International Guidelines 2018 PCOD Dr Sharda Jain , Dr Jyoti Agarwal Lifecare Centre
International Guidelines 2018 PCOD DIAGNOSTIC ASSESSMENT TOOLS + What we have learnt in last 50 years
OVERVIEW of PCOD
HISTORY
PREVALENCE
ETIOPATHOGENESIS as we understand it.
SYMTOMS & SIGNS
2018 GUIDELINES DIAGNOSTIC criteria, assessment, investigations , monitoring &
short / long term impact of untreated PCOD
This presentation briefly discuss the polycystic ovary syndrome in terms of pathogenesis, features and management. Then, It moves on to discuss the various guidelines laid down by Endocrine Society in 2013 for the management of patients with polycystic ovary syndrome.
Pcos by dr alka mukherjee dr apurva mukherjee nagpur m.s.alka mukherjee
Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine-metabolic disorder that implies various severe consequences to female health, including alarming rates of infertility. Although its exact etiology remains elusive, it is known to feature several hormonal disturbances, including hyperandrogenemia, insulin resistance (IR), and hyperinsulinemia. Insulin appears to disrupt all components of the hypothalamus-hypophysis-ovary axis, and ovarian tissue insulin resistance results in impaired metabolic signaling but intact mitogenic and steroidogenic activity, favoring hyperandrogenemia, which appears to be the main culprit of the clinical picture in PCOS. In turn, androgens may lead back to IR by increasing levels of free fatty acids and modifying muscle tissue composition and functionality, perpetuating this IR-hyperinsulinemia-hyperandrogenemia cycle. Nonobese women with PCOS showcase several differential features, with unique biochemical and hormonal profiles. Nevertheless, lean and obese patients have chronic inflammation mediating the long term cardiometabolic complications and comorbidities observed in women with PCOS, including dyslipidemia, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Given these severe implications, it is important to thoroughly understand the pathophysiologic interconnections underlying PCOS, in order to provide superior therapeutic strategies and warrant improved quality of life to women with this syndrome.
Polycystic Ovarian Syndrome is heterogeneous, multisystem endocrinopathy in women of reproductive age characterized by chronic anovulation resulting in infertility, irregular bleeding, obesity and hirsutism. Most common, although the least understood, cause of androgen excess. Initially it was described in 1935.Also known as Stein-Leventhal syndrome
The slide includes:
Introduction
Incidence
Pathophysiology
Pathology
Clinical features
Investigation
Treatment
International Guidelines 2018 PCOD Dr Sharda Jain , Dr Jyoti Agarwal Lifecare Centre
International Guidelines 2018 PCOD DIAGNOSTIC ASSESSMENT TOOLS + What we have learnt in last 50 years
OVERVIEW of PCOD
HISTORY
PREVALENCE
ETIOPATHOGENESIS as we understand it.
SYMTOMS & SIGNS
2018 GUIDELINES DIAGNOSTIC criteria, assessment, investigations , monitoring &
short / long term impact of untreated PCOD
This presentation briefly discuss the polycystic ovary syndrome in terms of pathogenesis, features and management. Then, It moves on to discuss the various guidelines laid down by Endocrine Society in 2013 for the management of patients with polycystic ovary syndrome.
The objectives of this report includes, introducing and looking at the overview of the topic of PCOS, the history of PCOS and what have we learnt about PCOS 1970-2018 etc.
Evidence linked treatment for endometriosis-associated infertilityApollo Hospitals
Endometriosis is conventionally defined as the presence of
tissue lesions or nodules that are histologically similar to
the endometrium, but are present at sites outside the uterus.It is a chronic, often recurring disease of complex and unclear aetiology. Endometriosis is a highly variable condition in terms of age and mode of presentation, range of symptoms, anatomical sites, response to treatment and likelihood of recurrence.
A Case Report on Intrahepatic Cholestasis of Pregnancyijtsrd
This case study is about a primigravida mother period of gestation 29 weeks and 5 days diagnosed with intrahepatic cholestasis of pregnancy IHCP . She had been married since 1 year and it is her first pregnancy. The patient is having gestational diabetes mellitus and hypothyroidism. The patients was admitted to antenatal ward of St. Stephen’s Hospital , New Delhi, with chief complaints of itching in palms, soles and over umbilical area since 2 weeks. During the physical examination the rashes were seen on abdomen, legs and breast. Per abdomen examination and ultrasound revealed that vertex presentation of the fetus and FHR as 136 min and fetal weight as 1923 gram and presence of low lying placenta. Routine blood examination revealed that patient was also a case of gestational diabetes mellitus and hypothyroidism. After all the required investigation she was diagnosed with IHCP with gestational diabetes mellitus and hypothyroidism. IHCP is a pregnancy related liver disorder characterized by pruritus, most often in the late second or early trimester of pregnancy and raised serum bile acids. The maternal outcome after treatment is fair but fetal outcomes becomes adverse in most of the conditions. Ms. Rana Kamar | Dr. Rajwant Randhawa | Dr. Priyanaka Choudhary "A Case Report on Intrahepatic Cholestasis of Pregnancy" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-6 | Issue-1 , December 2021, URL: https://www.ijtsrd.com/papers/ijtsrd49087.pdf Paper URL: https://www.ijtsrd.com/medicine/nursing/49087/a-case-report-on-intrahepatic-cholestasis-of-pregnancy/ms-rana-kamar
Science, practice and evidence are dynamic processes. This is typically vivid when it relates to Polycystic Ovarian Syndrome. PCOS is the commonest hyperandrogenic disorder in women and one of the most common causes of ovulatory infertility. Although polycystic ovaries were first described by the Italian scientist Vallisneri in 1721, it was largely forgotten until the 1930s, and then renamed after its rediscoverers as Stein-Leventhal syndrome. Even then, it still wasn’t until the invention of the ultrasound scanner in the 1980s and consensus of diagnosis in the early 1990s that PCOS was recognized on a wider scale in women of reproductive age. When attempting to diagnose with precision something that is complex, it is important that we first clearly define what it is we are trying to diagnose. PCOS is today seen as a heterogeneous syndrome where a range of symptoms may be present or absent, and may overlap with other conditions, it is perhaps best viewed as a spectrum of symptoms, pathologic findings and laboratory abnormalities. PCOS can be difficult to conceptualize, even for experts, as shown by the fact that there have been several different ways of diagnosing it over the years.
More recently, the fundamental role of hyperandrogenism has been pointed out.
However, PCOS compromises other pathological conditions that strongly modify the phenotype and play a dominant role in the pathophysiology of the disorder, including insulin resistance and hyperinsulinemia, obesity and metabolic disorders, all favoring together with androgen excess, an increased susceptibility to develop type 2 diabetes mellitus (T2DM) and, possibly, cardiovascular diseases. PCOS by itself may also have some genetic component as documented by familial aggregation and recent genetic studies. All the clinical features may however change throughout the lifespan, starting from adolescence to postmenopausal age. Therefore, PCOS should be considered as a lifetime disorder.
I sincerely hope that with the recommended readings attached and lecture, you will be able to strengthen your knowledge, thereby providing evidence-based medicine practice for the management of PCOS in a successful manner to improve and better women’s Health care. The best investment you can make is an investment in yourself. The more you learn, the more you’ll earn (Warren Buffett), so read as much as you can.
Thank You.
Regards: Rafi Rozan
cervical cancer is the worlds most leading cause for the death of women. so knowledge regarding that disease will help us to prevent that disease to some extent.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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2. Background
• PCOS 5% to 10% of women worldwide.
• This familial disorder appears to be inherited as a complex
genetic trait .
• It is characterized by a combination of
– Hyperandrogenism (either clinical or biochemical),
– Chronic anovulation and
– Polycystic ovaries.
• associated with
– Insulin resistance
– Obesity.
1.Endocrine disorder, PCOS In: Berek and Novaks Gynecology, Fifteen Edition , New Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
3. History
• In 1935, Irving F. Stein and Michael L. Leventhal first
described a symptom complex associated with anovulation.
• Stein and Leventhal described 7 patients (4 of whom were
obese) with amenorrhea; hirsutism; and enlarged, polycystic
ovaries.
Reproductive endocrinology, polycystic ovary in speroff’sendocrinology in gynecology , 7th edition ,walter wilkinsons pp
4. Diagnostic criteria
1990 Criteria (both 1 and 2) NIH
1. Chronic anovulation and
2. Clinical and/or biochemical signs of hyperandrogenism and
exclusion of other etiologies.
Revised 2003 criteria (2 out of 3)
1. Oligoovulation or anovulation
2. Clinical and/or biochemical signs of hyperandrogenism
3. Polycystic ovaries and exclusion of other etiologies
(congenital adrenal
hyperplasia, androgen-secreting tumors, Cushing’s syndrome)
From Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop
Group. Revised 2003 consensus on diagnostic criteria and long-term health risksrelated to polycystic ovary syndrome. Fertil Steril 2004;81:19–25
1.Endocrine disorder, PCOS In: Berek and
Novaks Gynecology, Fifteen Edition , New
Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
5. 1.Endocrine disorder, PCOS In: Berek and Novaks Gynecology, Fifteen Edition , New Delhi ,Wolter
Kluwer,2012 pp1075 t0 1090
6. • Other pathologies that can result in a POCS phenotype include
– Adult onset adrenal hyperplasia
– Adrenal or ovarian neoplasm
– Cushing syndrome
– Hypo- or hypergonadotropic disorders
– Hyperprolactinemia
– Thyroid disease
• Classically, the disorder is lifelong, characterized by abnormal
menses from puberty with acne and hirsutism arising in the
teens.
1.Endocrine disorder, PCOS In: Berek and Novaks Gynecology, Fifteen Edition , New Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
7. • It may arise in adulthood, concomitant with the
emergence of obesity.1
• PCOS is accompanied by increasing
hyperinsulinemia.1
• The sonographic criteria for PCO requires the
presence of 12 or more follicles in either ovary
measuring 2 to 9 mm in diameter and/or
increased ovarian volume (>10 mL).
• A single ovary meeting these criteria is
sufficient to affix the PCO diagnosis.1
1.Endocrine disorder, PCOS In: Berek and Novaks Gynecology, Fifteen Edition , New Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
8. Pathology
• Macroscopically, ovaries in women with
PCOS are two to five times the normal size.
• A cross-section of the surface of the ovary
discloses a white, thickened cortex with
multiple cysts that are typically less than a
centimeter in diameter.
• Microscopically, the superficial cortex is
fibrotic and hypocellular and may contain
prominent blood vessels.1
• The characteristics of the ovary reflect this
dysfunctional state
• The surface area is doubled, giving an average
volume increase of 2.8 times.
1.Endocrine disorder, PCOS In: Berek and
Novaks Gynecology, Fifteen Edition , New
Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
9. • The same number of primordial follicles is present, but the
number of growing and atretic follicles is doubled. Each ovary
may contain 20 to100 cystic follicles.
• The thickness of the tunica (outermost layer) is increased by
50%.
• A one-third increase in cortical stromal thickness and a 5-fold
increase in subcortical stroma are noted.
• The increased stroma is due both to hyperplasia of theca cells and
to increased formation subsequent to the excessive follicular
maturation and atresia.
• There are 4 times more ovarian hilus cell nests (hyperplasia).
1.Endocrine disorder, PCOS In: Berek and
Novaks Gynecology, Fifteen Edition , New
Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
10. 1.Endocrine disorder, PCOS In: Berek and
Novaks Gynecology, Fifteen Edition , New
Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
11. Pathophysiology and laboratory finding
• The hyperandrogenism and anovulation that accompany
PCOS may be caused by abnormalities in four
endocrinologically active compartments:
– (i) the ovaries
– (ii) the adrenal glands
– (iii) the periphery (fat)
– (iv) the hypothalamus–pituitary compartment
1.Endocrine disorder, PCOS In: Berek and
Novaks Gynecology, Fifteen Edition , New
Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
12. 1.Endocrine disorder, PCOS In: Berek and
Novaks Gynecology, Fifteen Edition , New
Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
• In patients with PCOS, the ovarian compartment is the most
consistent contributor of androgens.
• Dysregulation of CYP17, This hormone relates to ovarian
androgenic activity in PCOS in a number of ways.
– Total and free testosterone levels correlate directly with LH
levels.
– The ovaries are more sensitive to gonadotropic stimulation,
possibly as a result of CYP17 dysregulation.
– Gonadotropin-releasing hormone (GnRH) agonist effectively
suppresses serum testosterone and androstenedione levels.
– Larger doses of a GnRH agonist are required for androgen
suppression
13. • The peripheral compartment, defined as the skin and the
adipose tissue, manifests its contribution to the development of
PCOS in several ways.
– Aromatase and 17β-hydroxysteroid dehydrogenase activities are
increased in fat cells.
– The presence and activity of 5α-reductase in the skin largely
determines the presence or absence of hirsutism .
– With obesity the metabolism of estrogens is decreased.
– Whereas estradiol (E2) is at a follicular phase, estrone (E1) levels
are increased as a result of peripheral aromatization of
androstenedione.
– A chronic hyperestrogenic state, with reversal of the E1-to-E2
ratio, results and is unopposed by progesterone.
1.Endocrine disorder, PCOS In: Berek and Novaks Gynecology, Fifteen Edition , New Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
14. T h e hypothalamic–pituitary compartment participates in
aspects to the development of PCOS.
– An increase in LH pulse frequency relative to those in the
normal follicular phase is the result of increased GnRH pulse
frequency.
– This increase in LH pulse frequency explains the frequent
observation of an elevated LH and LH-to-FSH ratio.
– FSH is not increased with LH, likely because of the
combination of increased gonadotropin pulse frequency.
• About 25% of patients with PCOS exhibit mildly
elevated prolactin levels.
1.Endocrine disorder, PCOS In: Berek and Novaks Gynecology, Fifteen Edition , New Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
15. • Genetic studies of PCOS reported allele sharing in large
PCOS patient populations and linkage studies focused on
candidate genes most likely to be involved in the pathogenesis
of PCOS. These genes can be grouped in four categories:
– (i) insulin resistance–related genes
– (ii) genes that interfere with the biosynthesis and the action
of androgens
– (iii) genes that encode inflammatory cytokines.
– (iv) other candidate genes
1.Endocrine disorder, PCOS In: Berek and Novaks Gynecology, Fifteen Edition ,
New Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
16. Clinical consequences
1. Infertility.
2. Menstrual bleeding problems, ranging from amenorrhea to
dysfunctional uterine bleeding.
3. Hirsutism, alopecia, and acne.
4. An increased risk of cardiovascular disease.
5. An increased risk of diabetes mellitus in patients with insulin
resistance.
6. An increased risk of endometrial cancer and, perhaps, breast
cancer.
1.Endocrine disorder, PCOS In: Berek and
Novaks Gynecology, Fifteen Edition , New
Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
17. Infertility.
• The most common cause of oligo-ovulation and
anovulation among women presenting with infertility—is
polycystic ovarian syndrome (PCOS)
1.Endocrine disorder, PCOS In: Berek and
Novaks Gynecology, Fifteen Edition , New
Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
18. Menstrual bleeding problems
• The menstrual dysfunction in PCOS arises from anovulation
or oligo-ovulation.
• Ranges from amenorrhea to oligomenorrhea.
• Regular menses in the presence of anovulation in PCOS is
uncommon.
• one report found that among hyperandrogenic women with
regular menstrual cycles, the rate of anovulation is 21%
1.Endocrine disorder, PCOS In: Berek and
Novaks Gynecology, Fifteen Edition , New
Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
19. Hirsutism, alopecia, and acne.
• Hirsutism occurs in approximately 70% of patients with PCOS of
USA patient.
• Only 10% to 20% of patients with PCOS in Japan .
• A likely explanation for this discrepancy is the genetically
determined differences in skin 5α-reductase activity.
• Evaluation includes more than the assessment of the degree of
hirsutism done by Ferriman-Gallwey hirsutism scoring system.
• When hirsutism is moderate (>9) or severe or if mild hirsutism is
accompanied by features that suggest an underlying disorder,
elevated androgen levels should be ruled out.
1.Endocrine disorder, PCOS In: Berek and
Novaks Gynecology, Fifteen Edition , New
Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
20. Insulin resistance
• Patients with PCOS frequently exhibit insulin resistance and
hyperinsulinemia.
• Insulin resistance and hyperinsulinemia participate in the
ovarian steroidogenic dysfunction of PCOS.
• The most common cause of insulin resistance and
compensatory hyperinsulinemia is obesity.
• obesity has its frequent occurrence in PCOS, obesity alone
does not explain this important association
1.Endocrine disorder, PCOS In: Berek and
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Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
21. • Multiple other testing or screening scheme were proposed to assess
the presence of hyperinsulinemia and insulin resistance.
• In one, the fasting glucose-to-insulin ratio is determined, and values
less than 4.5 indicate insulin resistance.
• A peak insulin level of over 150 μIU/mL or a mean level of over 84
μIU/mL over the three blood draws of a 2-hour GTT as a criteria to
diagnoses hyperinsulinemia.
• Insulin resistance indicating an increased risk of diabetes mellitus
and cardiovascular disease.
• About one-third of obese PCOS patients have impaired glucose
tolerance (IGT), and 7.5% to 10% have type 2 diabetes mellitus.
1.Endocrine disorder, PCOS In: Berek and Novaks Gynecology, Fifteen Edition , New Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
22. • Interventions
• Two-Hour Glucose Tolerance Test Normal Glucose Ranges (World Health
Organization criteria, after 75-gm glucose load)
– Fasting 64 to 128 mg/dL
– One hour 120 to 170 mg/dL
– Two hour 70 to 140 mg/dL
• Two-Hour Glucose Values for Impaired Glucose Tolerance and Type 2
Diabetes
• (World Health Organization criteria, after 75-gm glucose load)
Normal (2-hour) <140 mg/dL
Impaired (2-hour) = 140 to 199 mg/dL
Type 2 diabetes mellitus (2-hour) ≥200 mg/dL
1.Endocrine disorder, PCOS In: Berek and
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Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
23. Metabolic Syndrome
• In addition to addressing the increased risk for diabetes.
• insulin resistance or hyperinsulinemia as a cluster syndrome called
metabolic syndrome or dysmetabolic syndrome X.
• The more dysmetabolic syndrome X criteria are present, the higher
the level of insulin resistance and its downstream consequences.
• Abnormal lipoproteins are common in PCOS.
• Obesity occurs in more than 50% of patients with PCOS.
• The body fat is usually deposited centrally (android obesity) and a
higher waist-to-hip ratio.
1.Endocrine disorder, PCOS In: Berek and
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Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
25. Acanthosis nigricans
• Acanthosis nigricans is a reliable marker of insulin
resistance in hirsute women.
• This thickened, pigmented, velvety skin lesion is most
often found in the vulva and may be present on the
axilla, over the nape of the neck, below the breast, and
on the inner thigh .
• The HAIR-AN syndrome consists of hyperandrogenism
(HA), insulin resistance (IR), and acanthosis nigricans
(AN).
1.Endocrine disorder, PCOS In: Berek and
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Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
26. Cancer
• In chronic anovulatory patients with PCOS, persistently
elevated estrogen levels.
• Uninterrupted by progesterone.
• Increase the risk of endometrial carcinoma.
• These endometrial cancers are usually well
differentiated, stage I lesions with a cure rate of more
than 90%.
• The risk of ovarian cancer is increased two- to
threefold in women with PCOS
1.Endocrine disorder, PCOS In: Berek and
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Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
27. Depression and Mood Disorders
• The clinical features of PCOS, such as infertility, acne,
hirsutism, and obesity, promote psychological morbidity.
• Women with PCOS face challenges to their feminine identity
that can lead to loss of self-esteem, anxiety, poor body image,
and depression.
1.Endocrine disorder, PCOS In: Berek and
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Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
28. Hyperandrogenic women be evaluated with the
following laboratory tests to exclude specific
causes and problems:
• Thyroid-stimulating hormone (TSH).
• Prolactin.
• Lipid and lipoprotein profile.
• Screen for Cushing's Disease if appropriate.
• Consider endometrial biopsy.
1.Endocrine disorder, PCOS In: Berek and
Novaks Gynecology, Fifteen Edition , New
Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
29. Mangement of pcos
• Conservative
– Weight loss
– Life style modification
• Medical
– Hyperandrogenism
• OCPS
• MPA
• Gnrh agonist
• Glucocorticoids
• Ketokonazole
• Spironolactone
• Cyproterone acetate
• Fenasteride
– Insulin resistance
• METFORMIN
31. Treatment of hyperandrogenism and PCOS
Weight Reduction
• Weight reduction is the initial recommendation for patients
with accompanying obesity
• it promotes health, reduces insulin, SHBG, and androgen
levels, and may restore ovulation either alone or combined
with ovulation-induction agents .
• Weight loss of as little as 5% to 7% over a 6- month period can
reduce the bioavailable or calculated free testosterone level
significantly and restore ovulation and fertility in more than
75% of women.
1.Endocrine disorder, PCOS In: Berek and
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Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
32. Oral Contraceptives
• Combination oral contraceptives (OCs) decrease adrenal
and ovarian androgen production and reduce hair growth in
nearly two-thirds of hirsute patients .
• The progestin component suppresses LH, resulting in
diminished ovarian androgen production.
• The estrogen component increases hepatic production of
SHBG, resulting in decreased free testosterone concentration.
• Estrogens decrease conversion of testosterone to DHT in the
skin by inhibition of 5α-reductase.
1.Endocrine disorder, PCOS In: Berek and
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Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
33. Medroxyprogesterone Acetate
• Oral or intramuscular administration of medroxyprogesterone
acetate (MPA) successfully treats hirsutism.
• It directly affects the hypothalamic–pituitary axis by
decreasing GnRH production and the release of gonadotropins,
thereby reducing testosterone and,estrogen production by the
ovary.
• Despite a decrease in SHBG, total and free androgen levels
are decreased significantly.
1.Endocrine disorder, PCOS In: Berek and
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Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
34. Gonadotropin-Releasing Hormone Agonists
• Administration of GnRH agonists may allow the differentiation
of androgen produced by adrenal sources from that of ovarian
sources .
• Treatment with leuprolide acetate given intramuscularly every
28 days decreases hirsutism and hair diameter in both idiopathic
hirsutism and hirsutism secondary to PCOS.
• Ovarian androgen levels are significantly and selectively
suppressed.
1.Endocrine disorder, PCOS In: Berek and
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Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
35. • Glucocorticoids
– Dexamethasone may be used to treat patients with PCOS
who have either adrenal or mixed adrenal and ovarian
hyperandrogenism.
– Doses of dexamethasone as low as 0.25 mg nightly or
every other night are used initially to suppress DHEAS
concentrations to less than 400 μg/dL.
• Ketoconazole
– Ketoconazole inhibits the key steroidogenic cytochromes.
– Administered at a low dose (200 mg per day), it can
significantly reduce the levels of androstenedione,
testosterone, and calculated free testosterone.1.Endocrine disorder, PCOS In: Berek and
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Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
36. Spironolactone
• specific antagonist of aldosterone, which competitively binds to the
aldosterone receptors in the distal tubular region of the kidney.
– Competitive inhibition of DHT at the intracellular receptor level.
– Suppression of testosterone biosynthesis by a decrease in the CYP
enzymes.
– Increase in androgen catabolism (with increased peripheral
conversion of testosterone to estrone).
– Inhibition of skin 5α-reductase activity.
• The most common dose is 50 to 100 mg twice daily.
1.Endocrine disorder, PCOS In: Berek and
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Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
37. Cyproterone Acetate
• Cyproterone acetate is a synthetic progestin derived from 17-OHP,
which has potent antiandrogenic properties.
• The primary mechanism of cyproterone acetate is competitive
inhibition of testosterone and DHT at the level of the androgen
receptor
• Administered in a reverse sequential regimen cyproterone acetate
100 mg per day on days 5 to 15, and ethinyl estradiol 30 to 50 mg
per day on cycle days 5 to 26.
• This cyclic schedule allows regular menstrual bleeding, provides
excellent contraception.
1.Endocrine disorder, PCOS In: Berek and
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Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
38. • Flutamide
• Flutamide, a pure nonsteroidal antiandrogen, is approved for
treatment of advanced prostate cancer.
• Its mechanism of action is inhibition of nuclear binding of
androgens in target tissues.
• Although it has a weaker affinity to the androgen receptor than
spironolactone or cyproterone acetate, larger doses (250 mg
given two or three times daily) may compensate for the
reduced potency.
1.Endocrine disorder, PCOS In: Berek and
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Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
39. Finasteride
• Finasteride is a specific inhibitor of type 2 5α-reductase
enzyme activity.
• In a study in which finasteride (5 mg daily) was compared
with spironolactone (100 mg daily), both drugs resulted in
similar significant improvement in hirsutism, despite differing
effects on androgen levels .
• Most of the improvement in hirsutism with finasteride
occurred after 6 months of therapy with 7.5 mg of finasteride
daily.
1.Endocrine disorder, PCOS In: Berek and
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Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
40. Insulin Sensitizers
• Because hyperinsulinemia appears to play a role in PCOS-
associated anovulation.
• Treatment with insulin sensitizers may shift the endocrine
balance toward ovulation and pregnancy, either alone or in
combination with other treatment modalities.
Metformin (Glucophage) is an oral biguanide
antihyperglycemic drug used extensively for non–insulin-
dependent diabetes.
1.Endocrine disorder, PCOS In: Berek and
Novaks Gynecology, Fifteen Edition , New
Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
41. • Metformin is pregnancy category B drug with no known human
teratogenic effect.
• It lowers blood glucose mainly by inhibiting hepatic
glucoseproduction and by enhancing peripheral glucose uptake.
• Metformin enhances insulin sensitivity at the postreceptor level and
stimulates insulin-mediated glucose disposal.
• Although the literature is conflicting, larger studies have suggested
that the live birth rate with metformin alone (7.2%) .
• Lower than that achieved with clomiphene, and the combination
does not confer additional benefit over clomiphene alone.
1.Endocrine disorder, PCOS In: Berek and
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Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
42. INFERTILITY DUE TO PCOS
• Ovulation Induction in Women with Polycystic Ovarian
Syndrome
• The goal of ovulation induction refers to the therapeutic
restoration of the release of one egg per cycle in a woman who
either has not been ovulating regularly or has not been
ovulating at all.
1.Endocrine disorder, PCOS In: Berek and
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Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
43. Clomiphene Citrate
• Clomiphene citrate is a weak synthetic estrogen that mimics
the activity of an estrogen antagonist when given at typical
pharmacologic doses for the induction of ovulation.
• It is cleared through the liver and excreted into the stool, with
85% clearance in 6 days.
• A functional hypothalamic–pituitary–ovarian axis is usually
required for appropriate clomiphene citrate action.
1.Endocrine disorder, PCOS In: Berek and
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Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
44. Clomiphene Citrate Outcomes
• Over the course of 6 months, clomiphene is associated with 49%
ovulation, 23.9% pregnancy, and 22.5% live birth rates in women
with anovulatory infertility.
• Multiple gestation rates with clomiphene citrate are approximately
8%, most of which are twins.
• Treatment should be limited to 6 ovulatory cycles or 12 total cycles.
• The drug is supplied in 50 mg tablets; the usual starting dose is 50
mg per day.
• Side effects of clomiphene citrate include vasomotor flushes, mood
swings, breast tenderness, pelvic discomfort, and nausea.
1.Endocrine disorder, PCOS In: Berek and
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Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
45. Tamoxifen
• Tamoxifen is an oral antiestrogen similar in structure to clomiphene
that is commonly used as an adjuvant therapy for breast cancer.
• Used off-label to induce ovulation.
• Ovulation and pregnancy rates are similar with tamoxifen and
clomiphene.
Aromatase Inhibitors
• These drugs include letrozole and anastrazole.
• The off-label use of letrozole for ovulation induction in clomiphene-
resistant patients was first reported in 2001
1.Endocrine disorder, PCOS In: Berek and
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Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
46. Gonadotropin Therapy
• Anovulatory PCOS patients who fail to ovulate or conceive with oral
agents should be considered for ovulation induction with exogenous
gonadotropin injections
• Typical protocols monitor at baseline, 4 to 5 days after treatment
initiation, then every 1 to 3 days until follicular maturation (expected
follicle growth is 1 to 2 mm daily after achieving 10 mm diameter)
• Given the goal of promoting growth of a single mature follicle, low
initial gonadotropin doses of 37.5 to 75 IU per day are generally
recommended
• Increases in doses by 50% of the previous dose after 7 days if no
follicle greater than 10 mm is observed
1.Endocrine disorder, PCOS In: Berek and
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Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
47. Contraindications to Gonadotropins for
the Treatment of Infertility in Women
1.Endocrine disorder, PCOS In: Berek and
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Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
1. Primary ovarian failure with elevated follicle-stimulating
hormone levels
2. Uncontrolled thyroid and adrenal dysfunction
3. An organic intracranial lesion such as a pituitary tumor
4. Undiagnosed abnormal uterine bleeding
5. Ovarian cysts or enlargement not caused by polycystic
ovary syndrome
6. Prior hypersensitivity to the particular gonadotropin
7. Sex hormone–dependent tumors of the reproductive tract
and accessory organs
8. Pregnancy
48. Risks of Exogenous Gonadotropin
Treatment
• Multiple Pregnancy
– Twin births have risen by more than 50% and births of triplet and
higher order multiple pregnancies have more than quadrupled since
1980.
– When compared to other anovulatory patients, PCOS patients using
gonadotropins are at higher risk for multiple gestations (36%),
• Ovarian Hyperstimulation Syndrome
– Ovarian hyperstimulation syndrome is an iatrogenic
complication of ovulation induction with exogenous
gonadotropins.
– ovarian hyperstimulation syndrome (4.6%).
• cycle cancellation (10%) because of their high numbers
of baseline antral follicles.
1.Endocrine disorder, PCOS In: Berek and Novaks Gynecology, Fifteen Edition , New Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
2.Reproductive endocrinology, polycystic ovary in speroff’sendocrinology in gynecology , 7th edition ,walter wilkinsons .
49. Ovarian Wedge Resection
• Bilateral ovarian wedge resection is associated with only a transient
reduction in androstenedione levels and a prolonged minimal decrease
in plasma testosterone .
• In patients with hirsutism and PCOS who had wedge resection, hair
growth was reduced by approximately 16% .
• Although Stein and Leventhal’s original report cited a pregnancy rate
of 85% following wedge resection and maintenance of ovulatory
cycles.
• subsequent reports show lower pregnancy rates and a concerning
incidence of periovarian adhesions Instances of premature ovarian
failure and infertility were reported.
1.Endocrine disorder, PCOS In: Berek and
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50. Laparoscopic Electrocautery
• Laparoscopic ovarian electrocautery
is used as an alternative to wedge
resection in patients with severe
PCOS whose condition is resistant to
clomiphene citrate.
• In a recent series, ovarian drilling was
achieved laparoscopically with an
insulated electrocautery needle, using
100-W cutting current to assist entry
and 40-W coagulating current to treat
each microcyst over 2 seconds (8-mm
needle in ovary)
1.Endocrine disorder, PCOS In: Berek and Novaks Gynecology, Fifteen Edition , New Delhi ,Wolter Kluwer,2012 pp1075 t0 1090
2.Jeffcoats gynecology
51. Recent advances
• LOS is used for ovulation induction in women
with PCOS after Clomiphene citrate failure.
• Evidence from RCT and metanalysis indicate
that LOS is as effective as gonadotrophins for
ovulation induction and has the advantage of
avoiding complication such as multiple
pregnancies and OHSS.
• Four punctures per ovary at 30w for 5seconds
per puncture using a monopolar diathermy
needle seems to be optimum amount of energy
required for LOS.
Laparoscopic ovarian surgery for polycystic ovarian sydrome in recent advances in obstetrics and gynecoogy 24th volume, churchill
livingstone, pp241.
52. • About 2/3rd of women ovulate after LOS and 50%
conceive within 12months
• About one third of the patients continue to
benefit from LOD for many years.
• Postoperative adhesion formation can be
minimized by avoiding thermal injury to the
ovarian surface and by ample irrigation.
• Women with BMI ≥ 35kg/m2 , testersterone ≥ 4.5
nmol/l, FAI15 and or infertility for >3year are
resistant to LOS
1.Endocrine disorder, PCOS In: Berek and
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Delhi ,Wolter Kluwer,2012 pp1075 t0 1090