Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Syndrome

Polycystic Ovary Syndrome

Cysts

Ovarian Cysts

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Gonadal Disorders

Endocrine System Diseases

Hypoglycemic Agents

All Drugs and Chemicals

Metformin

Progesterone

Progestins

Hormones

Hormone Antagonists

Women with PCOS initiating Metformin and exposure to vaginal progesterone for 6-8 days prior ro Endometrium Biopsy

Women with PCOS not planning initiating Metformin and exposure to vaginal progesterone for 6-8 days prior to Endometrium Biopsy

Women with PCOS who initiated metformin at least 3 months prior to enrollment who have completed a 6-10 day course of progesterone

once a day, 6-8 days as specified (prior to each EMBx)

Endometrin (progesterone 100mg vaginal inserts)

Lubna Pal, MBBS MRCOG MSc

The investigators aim is to conduct a prospective un-blinded pilot study of premenopausal women diagnosed with Polycystic Ovarian Syndrome (PCOS), defined using criteria developed at the 1990 NICHD conference on PCOS, undergoing treatment for ovulation induction with Metformin. We propose that improving insulin sensitivity with use of Metformin in women diagnosed with PCOS has facilitatory influences on the uterine endometrium.

Endometrial assessments are proposed following three month and then nine month treatment with metformin; expression of specified markers at respective time points will be compared to baseline.

Visit 1: Screening

* Signed informed consent
* Comprehensive history intake
* Physical exam: Vital signs, height, weight, waist circumferences, waist : hip ratio
* Urine pregnancy test
* Subjects provided with a 10 day supply of vaginal progesterone and EMBx will be scheduled between days 6-8 of progesterone use.

Visit 2: Baseline

* Urine pregnancy test
* Endometrium thickness will be measured via transvaginal ultrasound
* EMBx: sample of endometrial tissue will be sent for histopathology to rule out endometrial hyperplasia or cancer
* 20cc blood
* Metformin prescription and dispensing will be as per clinical care.
* Women will be advised to use barrier method of contraception (ie; condoms, contraceptive jellies or foam, sponge, diaphragm, or cervical cap) for the duration of the study.

Visits 3 and 5 (Weeks 8-10 and 30-34, respectively)

* Urine pregnancy test
* A 10 day course of vaginal progesterone to allow scheduling of EMBx's time points specified under visit 1

Visits 4 and 6 (Weeks 12 ± 1 week and 36 ± 1 week respectively)

- The procedure specified for baseline (Visit 2) will be repeated.

Endometrial Effects of Metformin Action in Women With Polycystic Ovarian Syndrome (PCOS)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Yale University

Immune System Diseases

Hypersensitivity

Ovarian Hyperstimulation Syndrome

All patients registered in this study will undergo natural cycle IVF with In Vitro maturation (IVM) performed on all immature retrieved oocytes.

In Vitro maturation

Avner Hershlag, MD

We hypothesize that the combination of natural cycle IVF or low dose gonadotropin injection combined with In Vitro Maturation (IVM) (Natural IVF/IVM) is a viable option for a selected population of infertility patients who cannot tolerate exogenous gonadotropins or are at risk of ovarian hyperstimulation syndrome.

Natural IVF/IVM may be an attractive treatment alternative to conventional controlled ovarian hyperstimulation (COH)/IVF treatment for infertile women in particular for a select group.

Natural IVF/IVM offers several advantages over conventional COH protocols for IVF including:

1. Elimination of the need for gonadotropin ovarian stimulation
2. Elimination of risk of developing OHSS
3. Simplification of treatment, eliminating the need for frequent blood tests and ultrasound monitoring
4. Reduced cost of treatment
5. Avoiding potential side effects of gonadotropins, including weight gain, bloating, breast tenderness, nausea, mood swings
6. Eliminates concerns about the potential risk of malignancy that may be associated with multiple cycles of ovarian stimulation in a predisposed population.

This pilot study will be conducted to assess the clinical efficacy of natural IVF/IVM

In Vitro Maturation (IVM) of Human Oocytes

Northwell Health

Follicle Stimulating Hormone

hCG primed in vitro maturation (IVM) procedure Gonadotropin is not used in this patient group If the endometrial thickness in 6mm or more and the mean diameter of largest follicle is 11 mm or less on menstrual cycle day 9 to 12 on ultrasonography, oocyte retrieval is planned two days later.

Recombinant hCG injection (priming) is given 36 hour before oocyte retrieval, followed by intracytoplasmic sperm injection (ICSI) for oocyte fertilization.

The biochemical pregnancy is confirmed by serum beta hCG 15 days later oocyte retrieval.

The clinical pregnancy is confirmed when gestational sac is detected by transvaginal ultrasonography 3 weeks later oocyte retrieval.

minimal stimulation IVF procedure These patients are stimulated with 150 or less IU of recombinant Follicle-stimulating hormone (FSH) from menstrual cycle day 3 in GnRH antagonist protocol.

If the mean diameters of two or more follicles are 17mm or more, oocyte retrieval is planned two days later.

Recombinant hCG is triggered 36 hour before oocyte retrieval, followed by intracytoplasmic sperm injection (ICSI) for oocyte fertilization if needed.

The biochemical pregnancy is confirmed by serum beta hCG 14 days later oocyte retrieval.

The clinical pregnancy is confirmed when gestational sac is detected by transvaginal ultrasonography 3 weeks later oocyte retrieval.

No gonadotropin is used, but hCG priming is utilized 36 hour before oocyte maturation.

IVF with minimal use of gonadotropin, i.e. 150 or less IU of recombinant FSH, followed by hCG triggering in GnRH antagonist protocol.

Minimal stimulation IVF

You Shin Kim, MD, PhD

Polycystic ovarian syndrome (PCOS) is most common endocrinologic disease in women of reproductive age with incidence of 6.6 \~ 8%. About fifty percent of the patients with PCOS manifest subfertility and significant proportion of these woman need assisted reproductive technology (ART). These patients are very sensitive to gonadotropins during conventional in vitro fertilization (IVF) and the risk of ovarian hyperstimulation syndrome (OHSS) is high. In vitro maturation (IVM) is an emerging alternative option to conventional IVF for minimizing the risk of OHSS in patients with PCOS. Until now, several studies has been reported the favorable outcomes of oocyte maturation rate, fertilization rate, clinical pregnancy rate, and live birth rate during IVM procedure. However, these results were from retrospective or observational study and there was no suitable randomized controlled trial (RCT).

Therefore, this prospective RCT is aimed to compare and analyze the clinical outcomes between IVM and minimal stimulation IVF in women with PCOS, assessing if IVM is recommendable clinical practice or not.

Polycystic ovarian syndrome (PCOS) is most common endocrinologic disease in women of reproductive age with incidence of 6.6 \~ 8%. About fifty percent of the patients with PCOS manifest subfertility and significant proportion of these women need assisted reproductive technology (ART). These patients are very sensitive to gonadotropins during conventional in vitro fertilization (IVF) and the risk of ovarian hyperstimulation syndrome (OHSS), an iatrogenic complication, is very high.

In vitro maturation (IVM) is has been suggested as an alternative option to conventional IVF for eliminating the risk of OHSS in patients with PCOS. In 1994, Trounson et al succeeded in fertilization of in vitro matured oocytes and transferring embryo during unstimulated IVF procedure in women with PCOS. Since then IVM was developed as one method of ART field.

Previously it had been reported that maturation rate of oocytes retrieved from patients with PCOS were lower than oocytes from women without PCOS. However, in several observational studies, maturation rate of oocytes was up to 80.3%, fertilization was up to 21.9%\~50% per cycle, and live birth rated was 15.9% per retrieval and 33% per cycle. And in several retrospective case-control studies of comparing IVM and conventional IVF, the miscarriage rate and ectopic pregnancy rate were similar, whereas the maturation rate of oocyte was up to 84%, fertilization rate was 43\~70% and pregnancy rate was 22\~56%. Because ovarian stimulation is not utilized, OHSS risk is preventable and cost is effective in IVM procedure.

Generally there are three types of IVM techniques; firstly, gonadotropin priming, in which technique small amount of gonadotropin is used for 3 to 5 days. Secondly, human chorionic gonadotropin (hCG) priming, in which hCG is used before oocyte retrieval. Thirdly, no gonadotropin and hCG priming is used. In gonadotropin-priming IVM technique, it had been reported that the number of retrieved oocytes were increased and pregnancy rate was improved from 0 to 29%, but there was no clear evidence of the efficacy. hCG priming technique, most commonly used technique, is for promoting meiotic resumption before full maturation of oocyte. The maturation rate of oocytes was 69\~84%, fertilization rate 45 \~ 80%, pregnancy rate 31 \~ 38.5% and live birth rate was 33% in the studies of investigating hCG priming IVM technique in women with PCOS.

Summarizing these observational and retrospective studies, it is expectable that IVM is promising ART method in patients with PCOS, minimizing the risk of OHSS with improved clinical pregnancy rate. However, there was no suitable randomized controlled trial (RCT) to confirm whether IVM is recommendable primary clinical ART practice to women with PCOS.

Therefore, this prospective RCT is aimed to compare and analyze the clinical outcomes between hCG-primed IVM protocol and minimal stimulation IVF with Gonadotropin-releasing hormone (GnRH) antagonist protocol in women with PCOS in fresh cycles.

Comparison of Clinical Outcomes Between IVM and Minimal Stimulation IVF in Patients With PCOS

Comparison of Clinical Outcomes Between in Vitro Maturation and Minimal Stimulation in Vitro Fertilization in Patients With Polycystic Ovarian Syndrome; Prospective, Randomized Controlled, Parallel, Open-label, Clinical Trial

Clinical pregnancy was determined by observation of a gestational sac with fetal heart beat by transvaginal ultrasound scan.

OHSS rate in each arm. Patients' symptoms (abdominal distension, bloating and pain, nausea, vomiting, palpitation) and ultrasonographic findings (fluid collection in pelvic and abdominal cavity, enlarged ovarian size) are investigated for OHSS detection.

CHA University

Associate professor

Nutritional and Metabolic Diseases

Overweight

Obesity

Insulin Resistance

Overnutrition

Nutrition Disorders

Body Weight

Hyperinsulinism

Metabolic Diseases

Glucose Metabolism Disorders

Central Nervous System Depressants

Other Dietary Supplements

Insulin

Insulin, Globin Zinc

Benzocaine

Tannic Acid

Participants will be randomized to an exercise training program or sedentary control group. The sedentary will not perform any structured physical activity or exercise. Participants will be encouraged to maintain their sedentary lifestyle and will be monitored by an accelerometer to track physical activity.

Participants will perform 12-weeks of aerobic exercise training

A progressive increase in duration, frequency and intensity so the last 8 weeks of exercise are performed for 60 min, 5 days per week and at 80% of aerobic capacity. The duration includes a 5 minute warm up and 5 minute cool down. All exercise will be performed on a stationary bicycle (i.e., cycle ergometer).

Aerobic Exercise Training

A goal of this study is to use a novel methodology to determine whether insulin resistance in women with polycystic ovary syndrome (PCOS) is related to the accumulation of proteins with modifications. This could lead to future research to determine if these modifications interfere with their proper function. Additionally, the investigators will determine how protein quality is affected by exercise training. Aerobic exercise enhances the endogenous oxidant buffering systems which may minimize oxidative damage to proteins. The investigators propose that aerobic exercise minimizes the accrual of modified proteins by increasing the synthesis of new proteins, but also by increasing the degradation and removal of old and damaged proteins. Based on our previous studies the investigators observed that insulin affects plasma protein synthesis and aerobic exercise improves insulin sensitivity not only in muscle but also in liver. The investigators therefore propose that aerobic exercise and related increase in insulin sensitivity (and decline in insulin levels) will reduce accumulation of old and modified skeletal muscle and plasma proteins leading to improved function.

Potential Impact of Polycystic Ovarian Syndrome on Protein Modifications and Accumulation

To determine the effect of 12 weeks of aerobic exercise training or sedentary behavior on insulin sensitivity measured by a 3 hour hyperinsulinemic-euglycemic clamp and response to a mixed-meal.

Alterations in protein modifications and accumulation will be measured by a novel methodology developed within our laboratory. Infusion of stable amino acid isotopes will be used to measure the accumulation of proteins before and after 12 weeks of aerobic exercise training or sedentary behavior. Plasma and muscle will be resolved using a two dimensional gel electrophoresis which will allow the identification of protein modifications and age.

Mayo Clinic

Principal Investigator

Diseases and Abnormalities at or Before Birth

Rare Diseases

Hyperandrogenism

Disorders of Sex Development

46, XX Disorders of Sex Development

Congenital Abnormalities

Urogenital Abnormalities

Adrenal Hyperplasia, Congenital

Adrenogenital Syndrome

Male Urogenital Diseases

Congenital Adrenal Hyperplasia

21-hydroxylase Deficiency

Anti-Infective Agents

Anti-Bacterial Agents

Androgens

Doxycycline

Antibiotics, Antitubercular

Matrix Metalloproteinase Inhibitors

Antimalarials

Antiprotozoal Agents

Antiparasitic Agents

Subjects randomized to receive doxycycline for a period of 12 weeks. A 12-week period thereafter will occur off study medication. The dose of doxycycline to be used in this study is 200mg/day in divided doses of 100mg twice daily. The dose of doxycycline being used in this study is 100mg because it is the standard approved dose.

The administered placebo is to be continued for a period of 12 weeks. A 12-week period thereafter will occur off placebo control

200mg/day in divided doses of 100mg twice daily

doxycycline

Sugar Pill

Kathleen M Hoeger, MD, MPH

Stephen Hammes, MD

The purpose of this study is to study the effect of a commonly used antibiotic, doxycycline, on the production of ovarian hormones and menstrual cycles in women with Polycystic Ovarian Syndrome (PCOS).

Polycystic ovarian syndrome (PCOS) is one of the leading causes of female infertility, affecting 5-10% of reproductive-age women . This heterogeneous disorder is characterized by anovulatory infertility, androgen excess, an increase in the ratio of LH to FSH, and morphologic polycystic changes to the ovaries. Obesity and insulin resistance are also metabolic factors associated with PCOS that further increase the morbidity in these patients. Inducing fertility in patients with PCOS can be a challenge, as it most often involves ovulation induction that can lead to ovarian enlargement, hyperstimulation, and multiple-birth pregnancies. This study is designed to determine novel effective strategies to promote normal cycling in this patient population.

Effect of a Commonly Used Antibiotic, Doxycycline, in Women With Polycystic Ovarian Syndrome

The Use of an MMP Inhibitor, Doxycycline, to Reduce Ovarian Androgen Production and Restore Normal Cycling in Women With Polycystic Ovarian Syndrome

We will determine total serum testosterone levels in all participating subjects at week 24.

We will determine total serum testosterone levels in all participating subjects at week 12.

Serum progesterone levels will be obtained on a weekly basis to assess ovulation. We will then perform statistical analysis on this data to determine the effectiveness of doxycycline in this study population.

The total number of ovulations per group. Ovulation was defined as elevation of serum progesterone and or urinary pregnanediol glucuronide followed by documented menstrual bleeding within 2 weeks of elevation.

University of Rochester

Professor

Subjects randomized to receive doxycycline for a period of 12 weeks. A 12-week period thereafter will occur off study medication. The dose of doxycycline to be used in this study is 200mg/day in divided doses of 100mg twice daily. The dose of doxycycline being used in this study is 100mg because it is the standard approved dose.

doxycycline: 200mg/day in divided doses of 100mg twice daily

The administered placebo is to be continued for a period of 12 weeks. A 12-week period thereafter will occur off placebo control

Sugar Pill: 1 pill twice a day

Total

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

total serum testosterone

free serum testosterone

serum hormone binding globulin (SHBG)

This study was underpowered due to reduced enrollment. Targeted enrollment was 40 and actual enrollment was 10.

Kathleen Hoeger MD MPH

in the sugar pill arm one participant dropped out at week 12

Total Serum Testosterone

This measurement was not completed, because the number of ovulations was measured in its place and better indicates the effect of the treatment. See outcome measure number 8.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Endometrial Effects of Metformin Action in Women With Polycystic Ovarian Syndrome (PCOS)	NCT01070160	Polycystic Ovar...	Endometrin (pro... Metformin	18 Years - 42 Years	Yale University
In Vitro Maturation (IVM) of Human Oocytes	NCT01843569	Polycystic Ovar... Patients Sensit... Ovarian Hyper S...	In Vitro matura...	25 Years - 42 Years	Northwell Health
Comparison of Clinical Outcomes Between IVM and Minimal Stimulation IVF in Patients With PCOS	NCT03134482	No Condition	IVM Minimal stimula...	20 Years - 39 Years	CHA University
Potential Impact of Polycystic Ovarian Syndrome on Protein Modifications and Accumulation	NCT02105428	Polycystic Ovar... Insulin Resista... Overweight Obese	Aerobic Exercis...	18 Years - 50 Years	Mayo Clinic
Effect of a Commonly Used Antibiotic, Doxycycline, in Women With Polycystic Ovarian Syndrome	NCT01788215	Polycystic Ovar... Irregular Menst... Androgen Excess	doxycycline Sugar Pill	18 Years - 40 Years	University of Rochester
In Vitro Maturation (IVM) of Human Oocytes	NCT01843569	Polycystic Ovar... Patients Sensit... Ovarian Hyper S...	In Vitro matura...	25 Years - 42 Years	Northwell Health
In Vitro Maturation (IVM) of Human Oocytes	NCT01843569	Polycystic Ovar... Patients Sensit... Ovarian Hyper S...	In Vitro matura...	25 Years - 42 Years	Northwell Health

Spots Global Cancer Trial Database for polycystic ovarian syndrome (pcos)