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

Antineoplastic Agents

All Drugs and Chemicals

Reproductive Control Agents

Letrozole

Progesterone

Chorionic Gonadotropin

Aromatase Inhibitors

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Progestins

Letrrozole 2.5 to 5 mg oral tablet cycle day 3-7.Pelvic ultrasound at cycle day 11 or 12 and repeat if needed until leading follicle is \>17 mm. Ovidrel 250 mcg injected sq. Timed intercourse or intrauterine insemination. No supplemental progesterone therapy in luteal phase

Letrrozole 2.5 to 5 mg oral tablet cycle day 3-7. Pelvic ultrasound at cycle day 11 or 12 and repeat if needed until leading follicle is \>17 mm. Ovidrel 250 mcg injected sq. Timed intercourse or intrauterine insemination.Crinone 8% (progesterone) vaginal therapy was provided in luteal phase for 14 days .Administration was started the second day after intrauterine insemination or timed intercourse.

progesterone supplementation for luteal phase support administered with vaginal applicators and used instead of progesterone intramuscular injections or progesterone vaginal suppositories.

Progesterone Vaginal Gel 8%

letrozole oral tablet 2.5 mg or 5 mg administered cycle day 3-7 for ovulation induction

Letrozole Oral Tablet

pelvic ultrasound performed at cycle day 11 or 12 and repeated as necessary until leading follicle size is \>17 mm in diameter

pelvic ultrasound

ovidrel 250 mcg given when leading follicle size is \> 17 mm in diameter

Ovidrel 250 MCG Per 0.5 ML Prefilled Syringe

Intrauterine insemination or timed intercourse (depending on semen parameters) performed 36-40 hours after Ovidrel

Intrauterine insemination or timed intercourse

Laurel A Stadtmauer, MD, PhD

Aromatase inhibitors such as letrozole are hypothesized to maintain normal hypothalamic/ pituitary feedback mechanisms and in the case of OI (ovulation induction) in women with PCOS, may act to increase follicular sensitivity to FSH by increasing intrafollicular androgen levels. Letrozole also may act to increase midluteal P levels presumably by induction of follicles and corpora lutea. The investigators are asking the question whether P supplementation with Crinone (8%) may have an additive beneficial effect on endometrial development in those women taking letrozole. Progesterone levels in the endometrium (tissue levels) have been documented to be significantly higher than serum levels after vaginal administration which may lead to higher pregnancy rates. In addition P has been shown to decrease LH pulse frequency which is elevated in PCOS and has been shown to down regulate endometrial androgen receptors. There have been retrospective studies showing progesterone supplementation seems to benefit both CC and letrozole treatment groups. In fact, this study showed the only pregnancies in the letrozole group were those in women who took P supplementation. However the number of cycles studied was small. There is a place for a randomized controlled trial (RCT) to determine if luteal phase P supplementation with Crinone should be used in all women using letrozole for Ovulation Induction (OI) in combination with Intrauterine Insemination (IUI) or Timed Intercourse (TI). This is currently not done in all clinical practices.

Approval of the study was obtained from the local IRB. Prospective volunteers had had an infertility workup including blood hormone levels (FSH, LH, E2, Progesterone, Prolactin, and Thyroid), partner's semen analysis, HSG, laparoscopy or hydrosonogram, plus a baseline evaluation including ultrasound of ovaries and uterus performed as standard of care. If the results of these tests and the remaining Inclusion/Exclusion criteria were met, the study consent was reviewed with participants and signatures were obtained. Participants contacted the clinic at the start of their menses (spontaneous or progesterone-induced) to start the treatment cycle. Eligibility criteria was reviewed, and Letrozole 2.5-7.5 mg day 3-7 was initiated based on BMI and prior response. An ultrasound was performed on cycle day 11 or 12 and repeated if needed to determine response until at least 1 follicle with mean diameter \> 17mm in size was observed. When the appropriate follicle size was reached, participants were randomized into one of the two treatment groups as determined by a randomization table, and Ovidrel (250mcg) was administered. If there was no response identified by follicle growth on day 21, the participant was considered a letrozole failure, the cycle was stopped, and the participant was dropped from the study and was not included in subsequent cycles.

IUI/TI was performed at 24-48 hours after the Ovidrel (hCG) injection. If the participant was randomized to progesterone (Crinone), the luteal phase was supplemented once daily with vaginal progesterone (Crinone 8%) starting the second day after the IUI or TI and continued for 14 days. A urine or serum pregnancy test was performed as standard of care 16 days after the IUI/TI. If the test was positive, a confirmatory blood level (βhCG) was performed as standard of care X2 (1 week apart) and an ultrasound on post-hCG day 35-42 was done. Any pregnancies occurring in either treatment group were followed for delivery outcomes. Information regarding the delivery (induced, vaginal, cesarean section), date of birth, infant measurements (weight and length) and other important information regarding the infant's condition was obtained. Participants were allowed to undergo up to 3 cycles of letrozole as the pregnancy rates for the first 3 cycles have been shown to be similar. The participants were re-randomized each cycle. If the participant was pregnant, Crinone (8%) was continued until 10 weeks gestation in both groups.

Each participant was able to proceed with up to 3 cycles (consecutively, if desired) of OI over the next 6 months and was re-randomized each cycle.

Participants who met criteria were randomized to either Crinone vaginal therapy versus no therapy in the luteal phase of an ovulation induction cycle. Participants who did not achieve a pregnancy were able to participate in up to 3 cycles, and were re-randomized with each cycle.

Data analysis was completed by blinded observer who had access only to participant ID number, cycle number and treatment, and pregnancy outcome

Vaginal Progesterone Supplementation in Women With PCOS Undergoing Ovulation Induction With Letrozole

"Supplementation of the Luteal Phase With Vaginal Progesterone (Crinone 8%) in Women With Polycystic Ovary Syndrome Undergoing Ovulation Induction With Letrozole: A Prospective and Randomized Controlled Trial

The primary endpoint of the trial is the Clinical Pregnancy Rate per cycle initiated

The secondary endpoint is the Live Birth Rate per cycle initiated (each cycle is 28 days)

Watson Pharmaceuticals

Eastern Virginia Medical School

Principal Investigator

Alkylating Agents

Participants who will receive gonadotoxic chemoradiation therapies to include the alkylating agents, heavy metals and plant alkaloids as a standard part of their cancer treatment. Participants will also receive the GnRHa for menstrual suppression as part of standard of care. Baseline blood draws and pelvic ultrasound will be the intervention. Repeat blood draws and pelvic ultrasound at 6 and 12 months will also be interventions.

Participants who will receive chemoradiation therapies presumed to be low risk for gonadotoxicity as determined by the literature and the patient's oncolologist as a standard part of their cancer treatment. Participants will also receive the GnRHa for menstrual suppression as part of standard of care. Baseline blood draws and pelvic ultrasound will be the intervention. Repeat blood draws and pelvic ultrasound at 6 and 12 months will also be interventions.

Blood draws will be performed immediately prior to GnRHa treatment and at 6 and 12 months following treatment completion

Blood draw

Pelvic ultrasound will be performed immediately prior to GnRHa treatment and at 6 and 12 months following treatment completion

Pelvic Ultrasound

This is a prospective case control study. Participants will be enrolled as case subjects or control subjects, depending upon the gonadotoxicity of their chemoradiation therapy. The chemotherapeutic regimens will be determined per standard of care. Participants will receive GnRHa (Lupron) as standard of care for menstrual suppression. Blood draws and pelvic ultrasound at baseline, 6 months and 12 months post completion of chemotherapy are the interventions. The duration of the study will be approximately 12 months.The study time includes the time necessary for completion of most cancer treatments in this population, which approximates 8-12 months, and time to allow complete excretion of the Lupron from the systemic circulation with reliable testing of the hypothalamic pituitary ovarian (H-P-O) axis. The results of the study will be used to guide a larger study evaluating the efficacy of gonadotropin releasing hormone agonist (GnRHa) as ovarian preservation therapy in young subjects receiving chemoradiation.

This study will not utilize a survey or questionnaire. Data will be collected via chart review and direct subject and/or guardian interviews.

Electronic medical records will be accessed only by approved clinical and research personnel to retrieve clinical and laboratory data.

At the initial visit, the following will be performed and collected on all subjects: Body Mass Index; age at thelarche; age at menarche; Tanner staging for breast and pubic hair; oncologic diagnosis; date of oncologic diagnosis; chemoradiation therapy treatment regimen; date of initiation of chemoradiation therapy; pre-treatment ovarian function blood tests; date GnRHa therapy initiated; a pelvic ultrasound will be performed to assess ovarian volumes and antral follicle count.

The subject will receive GnRHa 11.25 mg every 2 months until completion of chemotherapy, which is consistent with current clinical care at the University of Kentucky Medical Center (UKMC).

Study blood tests to evaluate ovarian function and pelvic ultrasound will be performed at three time points: immediately prior to initiation of GnRHa therapy and 6 and 12 months after chemoradiation therapy is completed.

The subject/guardian will be contacted by the study team at regular intervals to assess her progress and plan timing of study visits.

At subsequent visits, the investigator will record the date chemoradiation therapy treatment ended; date and reason GnRHa therapy discontinued; presence of breakthrough bleeding (BTB); timing of BTB in relation to most recent GnRHa injection. In order to document bleeding patterns, subjects will be asked to fill out the pictorial assessment of bleeding chart every month that they are in the study.

Six months after completion of chemoradiation therapy, the investigator will assess post-treatment ovarian function blood test levels and performed a pelvic U/S to assess ovarian volumes and antral follicle count. Investigator will as assess the resumption of spontaneous menses, parity, date of subject demise, if applicable.

Twelve months after completion of chemotherapy, we will assess post-treatment ovarian function blood test levels; and performed a pelvic U/S to assess ovarian volumes and antral follicle count. Investigator will as assess the resumption of spontaneous menses, parity, date of subject demise, if applicable.

GnRHA Therapy and Ovarian Preservation in Pediatric Cancer Patient

Gonadotropin Releasing Hormone Agonist (GnRHa) Therapy and Ovarian Preservation in Pediatric and Adolescent Subject Receiving Chemoradiation Therap

* UK IRB/Office of Research Integrity
* Law enforcement agencies when required by law
* University of Kentucky representatives
* UK Hospital
* ACOG
* Representatives of the National Cancer Institute (NCI), FDA, and other U.S. and international governmental regulatory agencies involved in overseeing research
* Authorized representatives at the University of Cincinnati who are collaborating on this research.
* Every research site of the study (including UK Healthcare and Cincinnati Children's and each site's research staff and medical staff)
* Every health care provider who provides services to you in connection with the study
* Any laboratories and other individuals and organizations that analyze your PHI in connection with the study
* The Sponsor and the people and companies they use to oversee, administer and/or conduct the study
* Kentucky Cancer Registry (KCR) to all follow-up assistance

Assess AMH change from baseline to 6 months.

Assess AMH change from baseline to 12 months.

Assess menstrual function change from baseline to 12 year.

Assess FSH change from baseline to 6 months.

Assess FSH change from baseline to 12 months.

Assess menstrual function change from baseline to 6 months.

To assess the agreement of AMH (\< or equal to 0.5 vs. \> 0.5) and AFC (\<16 follicles vs 16+ follicles) as indicators of ovarian reserve after chemoradiation and GnRHa therapy

University of Kentucky

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Consultation, Biological Test, Pelvic Ultrasound

Consultation in oncology: collection of oncological data and ongoing cancer treatments, clinical exam Consultation in gynecology: collection of gynecological data, contraception and reproductive medicine

Consultation

Blood test:

* FSH, LH, E2 and AMH
* 4 tubes of 7 mL

Biological Test

Audrey MAILLIEZ, MD

Christine DECANTER, MD

Interventional research with low risks and constraints, prospective and monocentric on the assessment of long-term fertility in patients who underwent an adjuvant sequential chemotherapy with or without a controled ovarian hyperstimulation. This study follows a previous one called NCT 01614704.

The patients will have a follow-up once a year during ten years beginning at the end of their chemotherapy.

They will have a consultation in oncology consisting of:

* a clinical exam,
* a collection and follow-up of oncological data
* a collection of ongoing cancer treatments

and a consultation in gynecology consisting of:

* a pelvic ultrasound scan (for AFC: Antral Follicle Count)
* a biological test (FSH, LH, E2, AMH)
* a collection of gynecological data, contraception and reproductive medicine

Follow-up of Sequential Chemotherapy and Stimulation for Fertility Preservation in Young Patients With Breast Cancer

Long-term Follow-up of Sequential Chemotherapy and Stimulation for Fertility Preservation in Young Patients Treated for a Breast Cancer

for patients who underwent adjuvant sequential chemotherapy of anthracycline and taxane separately, depending on whether or not they have had Controlled Ovarian Hyperstimulation

separately, depending on whether or not they have had Controlled Ovarian Hyperstimulation

describing the pregnancy type - number of pegnancies spontaneous versus assisted, with ot without the use of frozen gametes)

describing the pregnancy outcome : miscarriage or single or multiple birth separately, depending on whether or not they have had Controlled Ovarian Hyperstimulation

for patients who have had Controlled Ovarian Hyperstimulation

in terms of AMH rate depending on whether or not they have had Controlled Ovarian Hyperstimulation

in terms of Antral Follicle Count depending on whether or not they have had Controlled Ovarian Hyperstimulation

Survival without relapse defined by the time frame between the date of surgery and the date of the first recurrence

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Vaginal Progesterone Supplementation in Women With PCOS Undergoing Ovulation Induction With Letrozole	NCT03440359	Polycystic Ovar...	Progesterone Va... Letrozole Oral ... pelvic ultrasou... Ovidrel 250 MCG... Intrauterine in...	20 Years - 40 Years	Eastern Virginia Medical School
GnRHA Therapy and Ovarian Preservation in Pediatric Cancer Patient	NCT02677311	Cancer Chemoradiation	Blood draw Pelvic Ultrasou...	8 Years - 19 Years	University of Kentucky
Follow-up of Sequential Chemotherapy and Stimulation for Fertility Preservation in Young Patients With Breast Cancer	NCT03795246	Breast Cancer	Consultation Biological Test Pelvic Ultrasou...	18 Years -	Centre Oscar Lambret
Vaginal Progesterone Supplementation in Women With PCOS Undergoing Ovulation Induction With Letrozole	NCT03440359	Polycystic Ovar...	Progesterone Va... Letrozole Oral ... pelvic ultrasou... Ovidrel 250 MCG... Intrauterine in...	20 Years - 40 Years	Eastern Virginia Medical School

Spots Global Cancer Trial Database for pelvic ultrasound