Symptoms and General Pathology

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Neoplasms

Gland and Hormone Related Diseases

Syndrome

Infertility

Polycystic Ovary Syndrome

Genital Diseases

Urogenital Diseases

Cysts

Ovarian Cysts

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Gonadal Disorders

Endocrine System Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anticoagulants

Reproductive Control Agents

Gastrointestinal Agents

Other Dietary Supplements

Letrozole

Citric Acid

Sodium Citrate

Progesterone

Clomiphene

Enclomiphene

Zuclomiphene

Lactitol

Aromatase Inhibitors

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Citrate

70 women will receive urinary purified FSH (Fostimon® IBSA, Switzerland) 75IU daily for 7 days starting from the 3rd day of menstruation or progesterone withdrawal bleeding. If the follicle does not exceed 9 mm the dose will be increased by 37.5 IU every 7 days.

70 women will receive Letrozole (Femara®, Novartis, Switzerland) 2.5mg twice daily for 5 days starting from the 3rd day of menstruation or progesterone withdrawal bleeding.

75IU daily for 7 days starting from the 3rd day of menstruation or progesterone withdrawal bleeding. If the follicle does not exceed 9mm the dose will be increased by 37.5IU every 7 days

210 women with clomiphene resistant PCOS will be randomly divided into 3 equal groups using computer generated random numbers. Group 1 will receive FSH, group 2 will have Letrozole and group 3 will act as the control group with no intervention.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive age, with an incidence of 5 -10%. Classically clomiphene citrate (CC) is the first approach to induce ovulation in patients with PCOS. Although 70-80% of PCOS women can ovulate by the treatment with CC, only 40%of the PCOS women become pregnant. Women who do not ovulate with increasing doses of CC are described as being CC-resistant and remain a major challenge in gynecologic endocrinology. Traditional alternatives for CC-resistant patients include gonadotropin therapy and laparoscopic ovarian diathermy.

Gonadotropin therapy is widely used for ovulation induction in CC-resistant PCOS patients. The use of purified FSH preparation virtually free of LH activity, is a recommendable treatment since there is evidence that pure FSH may significantly reduce tonic LH levels, favourably alter the intraovarian hormonal milieu, and promote the initial follicular development with minimal risk of multiple follicular growth or ovarian hyperstimulation.

The use of metformin in PCOS is associated with cycle regulation, improved ovulation, and a reduction in circulating androgen levels. Metformin likely plays its role in improving ovulation induction in women with PCOS through a variety of actions, including reducing insulin levels and altering the effect of insulin on ovarian androgen biosynthesis, theca cell proliferation, and endometrial growth. In addition, potentially through a direct effect, it inhibits ovarian gluconeogenesis and thus reduces ovarian androgen production.

Letrozole is an orally-active aromatase inhibitor, with good potential for ovulation induction. Letrozole acts by reducing estrogen production by blocking androgens to estrogens conversion. Additionally, it has no adverse effect on endometrium and cervical mucus (7). This releases the pituitary from negative feedback of estrogens and releases FSH. Also, an added positive effect is increased follicular sensitivity to FSH through amplification of FSH receptor gene expression.

Hyper-insulinemia, which is closely associated with PCOS, is thought to be one of the causative factors for CC resistance. The prevalence of insulin resistance in PCOS is close to 50%.

All women with clomiphene resistant PCOS attending the subfertility clinic of Cairo university hospitals will be invited to participate in the study. PCOS diagnosis will be based on chronic anovulation and sonographic picture of polycystic ovaries (10). Clomiphene resistance will be defined as failure of ovulation in spite of receiving 150mg of clomiphene citrate for 5 days during the menstrual cycle.

Exclusion criteria are age \>40 years, other causes of infertility, hperprolactinaemia, allergy to FSH or metformin, previous FSH or LOD therapy, and body mass index (BMI)\>35.

The study will be explained to all the participants and a written informed consent will be obtained before participation.

Full history will be taken followed by complete examination and sonographic evaluation. Sonographic picture of polycystic ovaries will be defined when there are at least 12 follicles 2-9mm in the ovary and/or ovarian volume\>10cm3 (10) 210 women with clomiphene resistant PCOS will be randomly divided into 3 equal groups using computer generated random numbers. Group 1 will receive FSH, group 2 will have Letrozole and group 3 will act as the control group with no intervention.

Group 1 will receive urinary purified FSH (Fostimon® IBSA, Switzerland) 75IU daily for 7 days starting from the 3rd day of menstruation or progesterone withdrawal bleeding. If the follicle does not exceed 9mm the dose will be increased by 37.5IU every 7 days. The cycle will be cancelled if no follicles exceed 9mm 4 weeks after starting FSH. Group 2 will receive Letrozole (Femara®, Novartis, Switzerland) 2.5mg twice daily for 5 days starting from the 3rd day of menstruation or progesterone withdrawal bleeding.

Group 3 will have regular progesterone withdrawal bleeding in the form of norethisterone (stereonate® Hi Pharm, Egypt).

Serial vaginal ultrasound scans were done starting from the 10th day of menstruation, the frequency of monitoring will be individualized according to the women's response. When the dominant follicle reaches 17mm or more women will receive Human chorionic gonadotrophin (Choriomon® IBSA, Switzerland) 5000IU and a timed intercourse will be advised 36 hours later.

Comparison Between Letrozole and Urinary Purified FSH in Women With Clomiphene Citrate Resistant Polycystic Ovarian Syndrome.

Comparison Between Letrozole and Urinary Purified FSH in Women With Clomiphene Citrate Resistant Polycystic Ovarian Syndrome: A Randomised Controlled Trial

Regular vaginal ultrasounds will be done starting from the 8th day of starting the drug.

Cairo University

Lecturer of Gynecology and Obstetrics

Wounds and Injuries

Hyperthermia

Hypoglycemic Agents

Metformin

will receive urinary purified FSH (Fostimon® IBSA, Switzerland) 75IU daily for 7 days starting from the 3rd day of menstruation or progesterone withdrawal bleeding. If the follicle does not exceed 9mm the dose will be increased by 37.5IU every 7 days. The cycle will be cancelled if no follicles exceed 9mm 4 weeks after starting FSH. This was combined with oral metformin (Cidophage® CID, Egypt) 500 mg three times per day.

70 women will have laparoscopic ovarian drilling in which the ovaries will be stabilised by grasping the ovarian ligament and monopolar diathermy will be used to do 4-10 punctures in each ovary. The number of punctures will be individualised according to the size of the ovary. Serial vaginal ultrasound scans were done starting from the 10th day of menstruation, the frequency of monitoring will be individualized according to the women's response.

70 women will receive urinary purified FSH (Fostimon® IBSA, Switzerland) 75IU daily for 7 days starting from the 3rd day of menstruation or progesterone withdrawal bleeding. If the follicle does not exceed 9mm the dose will be increased by 37.5IU every 7 days. The cycle will be cancelled if no follicles exceed 9mm 4 weeks after starting FSH. This was combined with oral metformin (Cidophage® CID, Egypt) 500 mg three times per day

70 women will have LOD in which the ovaries will be stabilised by grasping the ovarian ligament and monopolar diathermy will be used to do 4-10 punctures in each ovary. The number of punctures will be individualised according to the size of the ovary. Serial vaginal ultrasound scans were done starting from the 10th day of menstruation, the frequency of monitoring will be individualized according to the women's response.

Laparoscopic ovarian drilling

AbdelGany MA Hassan

Nesreen AA Shehata, MD

AbdelGany MA Hassan, MRCOG, MD

210 women with clomiphene resistant PCOS will be randomly divided into 3 equal groups using computer generated random numbers. Group 1 will receive combined metformin and FSH, group 2 will have LOD and group 3 will act as the control group with no intervention.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive age, with an incidence of 5 -10% . Classically clomiphene citrate (CC) is the first approach to induce ovulation in patients with PCOS. Although 70-80% of PCOS women can ovulate by the treatment with CC, only 40%of the PCOS women become pregnant. Women who do not ovulate with increasing doses of CC are described as being CC-resistant and remain a major challenge in gynecologic endocrinology. Traditional alternatives for CC-resistant patients include gonadotropin therapy and laparoscopic ovarian diathermy.

Gonadotropin therapy is widely used for ovulation induction in CC-resistant PCOS patients. The use of purified FSH preparation virtually free of LH activity, is a recommendable treatment since there is evidence that pure FSH may significantly reduce tonic LH levels, favourably alter the intraovarian hormonal milieu, and promote the initial follicular development with minimal risk of multiple follicular growth or ovarian hyperstimulation .

The use of metformin in PCOS is associated with cycle regulation, improved ovulation, and a reduction in circulating androgen levels (5). Metformin likely plays its role in improving ovulation induction in women with PCOS through a variety of actions, including reducing insulin levels and altering the effect of insulin on ovarian androgen biosynthesis, theca cell proliferation, and endometrial growth. In addition, potentially through a direct effect, it inhibits ovarian gluconeogenesis and thus reduces ovarian androgen production .

Laparoscopic ovarian drilling (LOD) can avoid or reduce the need for gonadotropins for ovulation induction. Several potential mechanisms of action of LOD have also been suggested. The reduction of inhibin production following LOD is followed by an increase in FSH secretion and recruitment of a new cohort of follicles. Other theory is restoration of normal production of the putative gonadotropin surge after laparoscopic ovarian electrocautery. Moreover, drainage of androgens and inhibin from follicles surface may inhibit the excessive collagenisation of overlying ovarian cortex and facilitate Softening of ovarian tunica. Neighbouring follicles that are not undergoing atresia may then mature and gain access to the ovarian surface, facilitating ovulation. Initiation of normal inhibin B pulsatility by LOD appears to correlate with the postoperative onset of ovulatory cycles (3).

The main drawbacks of LOD are adhesions formation and ovarian atrophy. That is why minimising the number of diathermy points and avoiding diathermy near the ovarian hilum are recommended.

All women with clomiphene resistant PCOS attending the subfertility clinic of Cairo university hospitals will be invited to participate in the study. PCOS diagnosis will be based on chronic anovulation and sonographic picture of polycystic ovaries (8). Clomiphene resistance will be defined as failure of ovulation in spite of receiving 150mg of clomiphene citrate for 5 days during the menstrual cycle.

Exclusion criteria are age \>40 years, other causes of infertility, hyperprolactinaemia, allergy to FSH or metformin, previous FSH or LOD therapy, and body mass index (BMI)\>35.

The study will be explained to all the participants and a written informed consent will be obtained before participation.

Full history will be taken followed by complete examination and sonographic evaluation. Sonographic picture of polycystic ovaries will be defined when there are at least 12 follicles 2-9mm in the ovary and/or ovarian volume\>10cm3.

210 women with clomiphene resistant PCOS will be randomly divided into 3 equal groups using computer generated random numbers. Group 1 will receive combined metformin and FSH, group 2 will have LOD and group 3 will act as the control group with no intervention.

Group 1 will receive urinary purified FSH (Fostimon® IBSA, Switzerland) 75IU daily for 7 days starting from the 3rd day of menstruation or progesterone withdrawal bleeding. If the follicle does not exceed 9mm the dose will be increased by 37.5IU every 7 days. The cycle will be cancelled if no follicles exceed 9mm 4 weeks after starting FSH. This was combined with oral metformin (Cidophage® CID, Egypt) 500 mg tds.

Group 2 will have LOD in which the ovaries will be stabilised by grasping the ovarian ligament and monopolar diathermy will be used to do 4-10 punctures in each ovary. The number of punctures will be individualised according to the size of the ovary. Serial vaginal ultrasound scans were done starting from the 10th day of menstruation, the frequency of monitoring will be individualized according to the women's response.

When the dominant follicle reaches 17mm or more in either group, women will receive Human chorionic gonadotrophin (Choriomon® IBSA, Switzerland) 5000IU and a timed intercourse will be advised 36 hours later.

Group 3 will have regular progesterone withdrawal bleeding in the form of norethisterone (stereonate® Hi Pharm, Egypt).

Comparison Between Laparoscopic Ovarian Diathermy and Urinary Purified FSH in Women With Clomiphene Citrate Resistant Polycystic Ovarian Syndrome.

Comparison Between Laproscopic Ovarian Diathermy and Urinary Purified FSH in Women With Clomiphene Citrate Resistant Polycystic Ovarian Syndrome: A Randomised Controlled Trial

Vaginal sonography will be done regularly to check ovulation.

Pregnancy will be diagnosed by the presence of an intrauterine gestational sac on vaginal ultrasound scan one week after a missed period.

Androgens

Leuprolide

9 PCOS women will be studied. On study day one, r-FSH will be administered I.V. at a dose of 150 IU (FSH stimulation test). Blood samples will be obtained before and after FSH administration. After the FSH stimulation test, each subject will receive an I.M. injection of Lupron 3.75 mg. This dose has a duration effect of one month.

The FSH stimulation test will be repeated, as described above, at 5 weeks (early resumption of ovarian function) and 6 weeks (moderate resumption of ovarian function).

Women that participated in Phase I will be studied again after a washout of 2 months. On study day one, an FSH stimulation test will be performed as described above.

After the FSH stimulation test, each subject will receive an I.M. injection of Lupron 3.75 mg. This dose has a duration effect of one month. Four weeks after administration of Lupron, each subject will receive Letrozole 5mg for 14 days. The FSH stimulation test will be repeated at 5 weeks (early resumption of ovarian function) and 6 weeks (moderate resumption of ovarian function).

In Phase II, letrozole, 5 mg/day, will be given for 14 days

R. Jeffrey Chang, M.D.

The purpose of this study is to evaluate the effect of increased circulating androgens on estradiol production by the granulosa cells in response to FSH stimulus.

Various previous studies have demonstrated that androgens enhance granulosa cell function in a variety of animal species including rodents and non-human primates. In vitro studies have shown that granulosa cells exposed to either testosterone or dihydrotestosterone exhibit increased production of estrogen, progesterone and inhibin in response to FSH. Studies done in non-human primates have also shown that androgen increases the numbers of preantral and antral follicles as well as increases FSH receptor mRNA expression in granulosa cells. This suggests that granulosa cell hyperresponsiveness to FSH in polycystic ovary syndrome (PCOS) may be related to androgen excess. The investigators plan to address this possibility by performing a series of in vivo studies. In one of the investigator's prior studies androgen blockade was done by administration of flutamide and E2 responses to FSH assessed. This study has been completed and the manuscript is being prepared for publication. In the present protocol, the investigators propose to further study the role of androgens with a 2 phase study. In the first phase the investigators plan to suppress endogenous steroid hormone production by the ovaries via treatment with the GnRH analog Lupron for 4 weeks beyond which a gradual resumption of ovarian activity will occur. Granulosa cell (inhibin B) responses to FSH will be examined before and after ovarian suppression as well as during early and moderate recovery of ovarian steroidogenesis. These results will provide control data to which comparisons can be made from results of the next phase.

In the second phase, after a 2 month washout interval, the same subjects will again receive Lupron to suppress endogenous steroid production. After 4 weeks, at the beginning of ovarian activity resumption, the investigators will administer Letrozole 5mg for 14 days and again examine granulosa cell responses to FSH during recovery. Letrozole is a 3rd generation aromatase inhibitor which results in suppression of E2 production and increase in circulating serum androgen levels to about 40% greater than pre-treatment values. It is now also being used for ovulation induction. It has minimal side effects and is in general very well tolerated. By using Letrozole for 2 weeks after GnRH suppression of the ovaries, the investigators will more effectively increase the amount of circulating androgen while keeping estrogen at low levels, thereby allowing the investigators to more completely study the effects of isolated and elevated androgen levels on granulosa cell responses to FSH. By comparing results obtained in phase 1, the investigators will be able to determine if there is an androgen mediated response by granulosa cells to FSH stimulation in the absence of other ovarian steroids. Also, the addition of a control group will allow investigators to determine if the granulosa cell response is different between PCOS and normals.

It is hypothesized that there will be a significant rise in inhibin B production by the granulosa cells in PCOS women in response to FSH after treatment with Letrozole as compared to both the control group and to responses observed in the control phase of study. This would confirm that androgens are indeed responsible at least in part for the hyperresponsiveness to FSH seen in women with PCOS.

Effect of Increased Circulating Androgens on Granulosa Cell Responses to FSH.

Effect of Increased Circulating Androgens on Granulosa Cell Responses to FSH

Estradiol (pmol/L) measured during Phase I (without Letrozole) and during Phase II (with Letrozole) at time 24 hours during Week 0 and times 0 and 24 hours during Weeks 5 and 6 after FSH stimulation.

Inhibin B (ng/L) measured during Phase I (without Letrozole) and during Phase II (with Letrozole) at time 24 hours during Week 0 and times 0 and 24 hours during Weeks 5 and 6 after FSH stimulation.

LH and FSH (IU/L) measured during Phase I (without Letrozole) and during Phase II (with Letrozole) at time 24 hours during Week 0 and times 0 and 24 hours during Weeks 5 and 6 after FSH stimulation.

Testosterone, Androstenedione and 17-OH Progesterone (nmol/L) measured during Phase I (without Letrozole) and during Phase II (with Letrozole) at time 24 hours during Week 0 and times 0 and 24 hours during Weeks 5 and 6 after FSH stimulation.

University of California, San Diego

Professor Emeritus of Reproductive Medicine Division of Reproductive Endocrinology and Infertility

Phase I

Women that participated in Phase I will be studied again after a washout of 2 months. On study day one, an FSH stimulation test will be performed as described above.

After the FSH stimulation test, each subject will receive an I.M. injection of Lupron 3.75 mg. This dose has a duration effect of one month. Four weeks after administration of Lupron, each subject will receive Letrozole 5mg for 14 days. The FSH stimulation test will be repeated at 5 weeks (early resumption of ovarian function) and 6 weeks (moderate resumption of ovarian function).

Letrozole: In Phase II, letrozole, 5 mg/day, will be given for 14 days

Phase II

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Phase I - LH, FSH

Testosterone

Androstenedione

17-OH Progesterone

Phase I - Testosterone, Androstenedione, 17-OH Progesterone

Phase I - Estradiol

Phase II - LH, FSH

Phase II - Testosterone, Androstenedione, 17-OH Progesterone

Phase II - Estradiol

Dr. R. Jeffrey Chang

Phase I - Week 0 - 24 Hours

Phase I - Week 5 - 0 Hour

Phase I - Week 5 - 24 Hour

Phase I - Week 6 - 0 Hour

Phase I - Week 6 - 24 Hour

Phase II - Week 0 - 24 Hours

Phase II - Week 5 - 0 Hours

Phase II - Week 5 - 24 Hours

Phase II - Week 6 - 0 Hours

Phase II - Week 6 - 24 Hours

Estradiol During Phase I and Phase II

Inhibin B During Phase I and Phase II

LH and FSH During Phase I and Phase II

17OH-Progesterone

Testosterone, Androstenedione and 17-OH Progesterone During Phase I and Phase II

Phase I - All Study Participants

Overall Study - Phase I

Phase II - All Study Participants

Heart and Blood Diseases

Heart Arrest

Anovulation

usual administration of exogenous recombinant FSH

Didier R DEWAILLY, MD

We previously hypothesized that the excess of Anti-Mullerian Hormone (AMH) at the level of ovarian selectable follicles could be involved in the follicular arrest of Polycystic Ovary Syndrome (PCOS), mainly through inhibition of FSH effect on aromatase expression.In this study, we plan to investigate whether a drop in the serum AMH level would be concomitant to the appearance of a dominant follicle induced by administration of mild amounts of exogenous FSH in women with PCOS.

Women with PCOS (Rotterdam definition) whom anovulation is resistant to clomiphene citrate will receive recombinant FSH using the low-dose step-up protocol during only one cycle. Serum levels of estradiol, AMH, LH, FSH, inhibin B and ultrasound (U/S) parameters will be assessed twice a week until 3 days after appearance of \> 1 dominant follicle(s).The starting dose of recFSH will be 50 IU/day. In the absence of criteria for dominance (see below) after 14 days at 50 IU/day, recFSH dose will be increased by 25 IU/day every 7 days until dominance is achieved. Dominance will be defined by the appearance of at least one follicle \>10 mm growing at least 2 mm/day and serum E2\> 100 pg/L. Ultrsound examination will performed with a 7-MHz transvaginal transducer (Sonoline Elegra, Siemens), in real time, according to a standardized protocol.Serum AMH levels will be assessed using the second-generation enzyme immunoassay AMH-EIA.

Study of Mechanisms of Anovulation in Polycystic Ovary Syndrome

Dynamic Changes in the Serum Anti-Müllerian Hormone Level During Low-Dose recFSH Administration Further Support Its Role in the Anovulation of Polycystic Ovary Syndrome

Organon

University Hospital, Lille

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Comparison Between Letrozole and Urinary Purified FSH in Women With Clomiphene Citrate Resistant Polycystic Ovarian Syndrome.	NCT02304107	Infertility	FSH Letrozole	20 Years - 40 Years	Cairo University
Comparison Between Laparoscopic Ovarian Diathermy and Urinary Purified FSH in Women With Clomiphene Citrate Resistant Polycystic Ovarian Syndrome.	NCT02304536	Infertility	FSH Laparoscopic ov...	20 Years - 40 Years	Cairo University
Comparison Between Laparoscopic Ovarian Diathermy and Urinary Purified FSH in Women With Clomiphene Citrate Resistant Polycystic Ovarian Syndrome.	NCT02304536	Infertility	FSH Laparoscopic ov...	20 Years - 40 Years	Cairo University
Effect of Increased Circulating Androgens on Granulosa Cell Responses to FSH.	NCT02389088	Polycystic Ovar...	Letrozole	18 Years - 40 Years	University of California, San Diego
Study of Mechanisms of Anovulation in Polycystic Ovary Syndrome	NCT00492882	Anovulation	usual administr...	18 Years - 40 Years	University Hospital, Lille

Spots Global Cancer Trial Database for fsh

Every month we try and update this database with for fsh cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for fsh

Every month we try and update this database with for fsh cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for fsh cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.