Review

Authors: Rumaisa Rashid, Suhail Ahmad Mir, Ozaifa Kareem...

Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women is characterized by polycystic ovaries, chronic anovulation and hyperandrogenism. The treatment in PCOS is mainly symptomatic and involves lifestyle interventions and medications such as Metformin, Oral contraceptives and Antiandrogens. However, the management of PCOS is challenging and current interventions are not able to deal with outcomes of this syndrome. This review encompasses latest pharmacotherapeutic and non-pharmacotherapeutic interventions currently in use to tackle various symptomatic contentions in PCOS. Our focus has been mainly on novel therapeutic modalities for treatment/management of PCOS, like use of newer insulin sensitizers viz., Inositols, Glucagon-like peptide-1(GLP-1) agonists, Dipeptidyl pepdidase-4 (DPP-4) inhibitors, and sodium-glucose transport protein 2 (SGLT2) inhibitors. Also, evidence suggesting the use of vitamin D, statins, and Letrozole as emerging therapies in PCOS have been summarized in this review. Additionally, novel cosmetic techniques like electrolysis, laser and use of topically applied eflornithine to tackle the most distressing feature of facial hirsutism associated with PCOS, non-pharmacological therapy like acupuncture and the role of herbal medicine in PCOS management have also been discussed.

Topics: Acupuncture; Anovulation; Eflornithine; Female; Herbal Medicine; Hirsutism; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperandrogenism; Hypoglycemic Agents; Laser Therapy; Letrozole; Metformin; Polycystic Ovary Syndrome; Vitamin D

PubMed: 35181044
DOI: 10.1016/j.tjog.2021.11.009

Authors: Susanna Marinelli, Gabriele Napoletano, Marco Straccamore...

Obesity has been associated with reduced fertility, although the dynamics and mechanisms which link excess weight to reduced fertility are not yet fully clarified. Obese women, especially those with central obesity, are less likely to conceive per cycle. Obese women suffer from perturbations of the hypothalamus-pituitary-ovary axis, disturbances of the menstrual cycle and are up to three times more likely to suffer from oligo/anovulation. A delicate hormonal balance regulates follicular development and the maturation of oocytes and it has been observed that obesity can alter the hormonal environment: adipocytes, in fact, are responsible for the production of a hormone called leptin (present in high quantities in obese women) which has been associated with reduced fecundity. In addition to compromising ovulation, obesity negatively affects the development and implantation of the endometrium. The expression of polycystic ovary syndrome (PCOS) is regulated, in part, by weight, so obese women with PCOS often have a more severe phenotype and higher subfertility rates. Furthermore, obesity impairs women's response to medically assisted procreation (MAP) treatments. The authors have set out to delineate a broad-ranging overview of obesity's impact on female fertility, by drawing upon sources spanning the 1994-2022 period. Assisted reproductive technology (ART) procedures are also discussed as they relate to obese patients. In addition the dynamics by which maternal obesity reportedly affects fetal, neonatal and child development have also been briefly enunciated.

Topics: Anovulation; Female; Fertility; Humans; Infertility, Female; Obesity; Polycystic Ovary Syndrome; Pregnancy

PubMed: 36043953
DOI: 10.23750/abm.v93i4.13466

Review

Authors: Ying-Yi Luan, Lei Zhang, Yi-Qiu Peng...

A polycystic ovarian syndrome (PCOS) is the most common endocrine disorder affecting females. Furthermore, it is a heterogeneous disease with a variety of etiologies and outcomes. Patients frequently complain about infertility, irregular menstruation, acne, seborrheic dermatitis, hirsutism, and obesity. PCOS can be caused by hypothalamic-pituitary-ovarian axis dysfunction, heredity, or metabolic abnormalities. PCOS is characterized by chronic low-level inflammation, which includes an imbalance in pro-inflammatory factor secretion, endothelial cell dysfunction, and leukocytosis. PCOS is also distinguished by hormonal and immune dysregulation. During PCOS, immune cells and immune regulatory molecules play critical roles in maintaining metabolic homeostasis and regulating immune responses. Because of oligo/anovulation, patients with PCOS have low progesterone levels. Therefore, low progesterone levels in PCOS overstimulate the immune system, causing it to produce more estrogen, which leads to a variety of autoantibodies. This review aims to summarize the immune regulation involved in the pathogenesis of PCOS and pave the way for the development of better PCOS treatment options in the near future.

Topics: Anovulation; Female; Hirsutism; Humans; Hyperandrogenism; Polycystic Ovary Syndrome; Progesterone

PubMed: 35447143
DOI: 10.1016/j.cca.2022.04.234

Review

Authors: Ewa Rudnicka, Michał Kunicki, Anna Calik-Ksepka...

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-aged women. It is characterized by chronic anovulation, hyperandrogenism, and the presence of polycystic ovary in ultrasound examination. PCOS is specified by an increased number of follicles at all growing stages, mainly seen in the preantral and small antral follicles and an increased serum level of Anti-Müllerian Hormone (AMH). Because of the strong correlation between circulating AMH levels and antral follicle count on ultrasound, Anti-Müllerian Hormone has been proposed as an alternative marker of ovulatory dysfunction in PCOS. However, the results from the current literature are not homogeneous, and the specific threshold of AMH in PCOS and PCOM is, therefore, very challenging. This review aims to update the current knowledge about AMH, the pathophysiology of AMH in the pathogenesis of PCOS, and the role of Anti-Müllerian Hormone in the treatment of this syndrome.

Topics: Anovulation; Anti-Mullerian Hormone; Female; Humans; Hyperandrogenism; Ovarian Follicle; Polycystic Ovary Syndrome; Ultrasonography

PubMed: 34830389
DOI: 10.3390/ijms222212507

Authors: Seda Hanife Oguz, Bulent Okan Yildiz

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

Clinical Trial

Authors: Chunzhu Li, Chuan Xing, Jiaqi Zhang...

BACKGROUND

Time-restricted feeding (TRF) is a form of intermittent fasting, which is beneficial for weight loss and cardiometabolic health. Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine and metabolic diseases affecting women of childbearing age. It is associated with an increased prevalence of metabolic syndrome, cardiovascular diseases and type 2 diabetes. The effects of TRF on PCOS patients remains undefined, here we investigated the impact of TRF on women with anovulatory PCOS.

METHODS

Eighteen PCOS women aged between 18 and 31 with anovulation participated in a 6-week trial which were divided into two consecutive periods: (1) 1-week baseline weight stabilization period and (2) 5-week TRF period. Fifteen participants completed the study. Changes in body weight, body mass index (BMI), Waist-to-Hip Ratio, skeletal muscle mass, body fat mass (BFM), body fat percentage (BF%), visceral fat area (VFA), luteinizing hormone (LH), follicle-stimulating hormone (FSH), LH/FSH, total testosterone (TT), sex hormone-binding globulin (SHBG), free androgen index (FAI), fasting glucose, fasting insulin (FINS), homeostasis model assessment-insulin resistance (HOMA-IR), area under the curve (AUC) for insulin (AUCIns), area under the curve (AUC) for glucose (AUCGlu), AUCIns/AUCGlu Ratio, lipids, uric acid, alanine aminotransferase (ALT), aspartate aminotransferase, high-sensitivity C-reactive protein (hsCRP), insulin-like growth factor (IGF-1), menstrual cycle and eating behaviors were evaluated.

RESULTS

Significant changes in body weight, BMI, BFM, BF%, VFA, TT, SHBG, FAI, FINS, HOMA-IR, AUCIns, AUCIns/AUCGlu Ratio, ALT, hsCRP and IGF-1 were found after the TRF period. An improvement in menstrual cycle irregularity was detected in 73.3% (11/15) patients.

CONCLUSION

The diet of TRF may be beneficial to anovulatory PCOS on weight loss especially reducing body fat, improving menstruation, hyperandrogenemia, insulin resistance and chronic inflammation. Trial registration Clinicaltrial.gov, NCT04580433, registered October 8, 2020, https://clinicaltrials.gov/ct2/show/NCT04580433.

Topics: Adolescent; Adult; Anovulation; Body Mass Index; Diabetes Mellitus, Type 2; Fasting; Female; Humans; Insulin; Insulin Resistance; Metabolome; Polycystic Ovary Syndrome; Young Adult

PubMed: 33849562
DOI: 10.1186/s12967-021-02817-2

Review

Authors: Emilie Steentoft Dahlberg, Dorte Andersen, Pernilla Skjødt Andersson...

This review describes the current evidence regarding the putative indications of letrozole (LTZ) in fertility treatment. Prior to intrauterine insemination, LTZ is recommended in women with normogonadotrophic oligo-anovulation. In ovulatory women, LTZ is equal to clomiphene and may be used instead of exogenous gonadotrophin. LTZ may be used as co-treatment in poor responders prior to in vitro fertilization/intracytoplasmic sperm injection. In addition, LTZ prior to frozen-thawed embryo transfer is increasingly used in women with normogonadotrophic oligo-anovulation.

Topics: Male; Female; Humans; Letrozole; Anovulation; Fertility Agents, Female; Semen; Clomiphene

PubMed: 37873987
DOI: No ID Found

Review

Authors: Sebastian Franik, Quang-Khoi Le, Jan Am Kremer...

BACKGROUND

Polycystic ovary syndrome (PCOS) is the most common cause of infrequent periods (oligomenorrhoea) and absence of periods (amenorrhoea). It affects about 5% to 20% of women worldwide and often leads to anovulatory infertility. Aromatase inhibitors (AIs) are a class of drugs that were introduced for ovulation induction in 2001. Since about 2001 clinical trials have reached differing conclusions as to whether the AI, letrozole, is at least as effective as the first-line treatment clomiphene citrate (CC), a selective oestrogen receptor modulator (SERM).

OBJECTIVES

To evaluate the effectiveness and safety of AIs (letrozole) (with or without adjuncts) compared to SERMs (with or without adjuncts) for infertile women with anovulatory PCOS for ovulation induction followed by timed intercourse or intrauterine insemination.

SEARCH METHODS

We searched the following sources, from their inception to 4 November 2021, to identify relevant randomised controlled trials (RCTs): the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase and PsycINFO. We also checked reference lists of relevant trials, searched the trial registers and contacted experts in the field for any additional trials. We did not restrict the searches by language or publication status.

SELECTION CRITERIA

We included all RCTs of AIs used alone or with other medical therapies for ovulation induction in women of reproductive age with anovulatory PCOS.

DATA COLLECTION AND ANALYSIS

Two review authors independently selected trials, extracted the data and assessed risks of bias using RoB 1. We pooled trials where appropriate using a fixed-effect model to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for most outcomes, and risk differences (RDs) for ovarian hyperstimulation syndrome (OHSS). The primary outcomes were live birth rate and OHSS rate. Secondary outcomes were clinical pregnancy, miscarriage and multiple pregnancy rates. We assessed the certainty of the evidence for each comparison using GRADE methods.

MAIN RESULTS

This is a substantive update of a previous review; of six previously included trials, we excluded four from this update and moved two to 'awaiting classification' due to concerns about validity of trial data. We included five additional trials for this update that now includes a total of 41 RCTs (6522 women). The AI, letrozole, was used in all trials. Letrozole compared to SERMs with or without adjuncts followed by timed intercourse Live birth rates were higher with letrozole (with or without adjuncts) compared to SERMs followed by timed intercourse (OR 1.72, 95% CI 1.40 to 2.11; I = 0%; number needed to treat for an additional beneficial outcome (NNTB) = 10; 11 trials, 2060 participants; high-certainty evidence). This suggests that in women with a 20% chance of live birth using SERMs, the live birth rate in women using letrozole with or without adjuncts would be 27% to 35%. There is high-certainty evidence that OHSS rates are similar with letrozole or SERMs (0.5% in both arms: risk difference (RD) -0.00, 95% CI -0.01 to 0.01; I = 0%; 10 trials, 1848 participants; high-certainty evidence). There is evidence for a higher pregnancy rate in favour of letrozole (OR 1.69, 95% CI 1.45 to 1.98; I = 0%; NNTB = 10; 23 trials, 3321 participants; high-certainty evidence). This suggests that in women with a 24% chance of clinical pregnancy using SERMs, the clinical pregnancy rate in women using letrozole with or without adjuncts would be 32% to 39%. There is little or no difference between treatment groups in the rate of miscarriage per pregnancy (25% with SERMs versus 24% with letrozole: OR 0.94, 95% CI 0.66 to 1.32; I = 0%; 15 trials, 736 participants; high-certainty evidence) and multiple pregnancy rate (2.2% with SERMs versus 1.6% with letrozole: OR 0.74, 95% CI 0.42 to 1.32; I = 0%; 14 trials, 2247 participants; high-certainty evidence). However, a funnel plot showed mild asymmetry, indicating that some trials in favour of SERMs might be missing.  Letrozole compared to laparoscopic ovarian drilling (LOD) One trial reported very low-certainty evidence that live birth rates may be higher with letrozole compared to LOD (OR 2.07, 95% CI 0.99 to 4.32; 1 trial, 141 participants; very low-certainty evidence). This suggests that in women with a 22% chance of live birth using LOD with or without adjuncts, the live birth rate in women using letrozole with or without adjuncts would be 24% to 47%. No trial reported OHSS rates. Due to the low-certainty evidence we are uncertain if letrozole improves pregnancy rates compared to LOD (OR 1.47, 95% CI 0.95 to 2.28; I² = 0%; 3 trials, 367 participants; low-certainty evidence). This suggests that in women with a 29% chance of clinical pregnancy using LOD with or without adjuncts, the clinical pregnancy rate in women using letrozole with or without adjuncts would be 28% to 45%. There seems to be no evidence of a difference in miscarriage rates per pregnancy comparing letrozole to LOD (OR 0.65, 95% CI 0.22 to 1.92; I² = 0%; 3 trials, 122 participants; low-certainty evidence). This also applies to multiple pregnancies (OR 3.00, 95% CI 0.12 to 74.90; 1 trial, 141 participants; very low-certainty evidence).

AUTHORS' CONCLUSIONS

Letrozole appears to improve live birth rates and pregnancy rates in infertile women with anovulatory PCOS, compared to SERMs, when used for ovulation induction, followed by intercourse. There is high-certainty evidence that OHSS rates are similar with letrozole or SERMs. There was high-certainty evidence of no difference in miscarriage rate and multiple pregnancy rate. We are uncertain if letrozole increases live birth rates compared to LOD. In this update, we added good quality trials and removed trials with concerns over data validity, thereby upgrading the certainty of the evidence base.

Topics: Abortion, Spontaneous; Anovulation; Aromatase Inhibitors; Clomiphene; Female; Fertility Agents, Female; Humans; Infertility, Female; Letrozole; Live Birth; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Selective Estrogen Receptor Modulators

PubMed: 36165742
DOI: 10.1002/14651858.CD010287.pub4

Review

Authors: Diana Hamilton-Fairley, Alison Taylor

Topics: Anovulation; Body Weight; Electrocoagulation; Female; Hormones; Humans; Hyperprolactinemia; Hypogonadism; Hypothyroidism; Infertility, Female; Menopause, Premature; Ovulation Induction; Polycystic Ovary Syndrome

PubMed: 12958117
DOI: 10.1136/bmj.327.7414.546

Authors: Sarah L Berga

Topics: Androgens; Anovulation; Brain; Female; Humans; Hyperandrogenism; Phenotype; Polycystic Ovary Syndrome

PubMed: 35971943
DOI: 10.1080/09513590.2022.2106475