Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Carcinoma, Ductal, Breast

Carcinoma, Ductal

Breast Diseases

Skin Diseases

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

All Drugs and Chemicals

Hormones

Follicle Stimulating Hormone

Degarelix injection(s)

Michaël GRYNBERG, MD, PhD

The present investigation aims to evaluate the efficacy of an innovative protocol of controlled ovarian stimulation for breast cancer patients, who are candidates for fertility preservation.

Currently, vitrification of oocytes and/or embryos after controlled ovarian stimulation is the most established method for female fertility preservation. However, this stimulation induces an increase in serum estrogen levels, which is theoretically problematic in case of hormone-sensitive tumors such as breast cancer. The majority of oncology teams accept, in very specific situations (particularly when the tumor has been surgically removed), this ovarian stimulation, because the expected benefits of fertility preservation far outweigh the risks. However, everyone agrees that it would be more comfortable to be able to offer vitrification of oocytes and/or embryos using ovarian stimulation without increasing estrogen levels.

In this research, investigators will evaluate the efficacy of degarelix (Firmagon®), currently indicated for the treatment of prostate cancer, as an innovative ovarian stimulation procedure. Administered at the beginning of ovarian stimulation, they believe it should maintain serum estradiol levels at physiological values at the end of stimulation.

Recent improvements in freezing techniques have led to the development of fertility preservation techniques for young women diagnosed with cancer. Currently, vitrification of oocytes or embryos after controlled ovarian stimulation (COS) represents the only established method. This COS is based on the daily administration of exogenous Follicle Stimulating Hormone (FSH) and an ovulation blockage using Gonadotropin Releasing Hormone (GnRH) antagonists (0.25 mg/d) initiated after approximately 6 days of stimulation and continued until ovulation is triggered.

In addition to requiring 15 days, COS induces supraphysiological hyperestradiolaemia (5-10 times normal) which can be problematic in case of hormone-sensitive tumors such as breast cancer. The majority of oncology teams accept, in very specific situations (particularly when the tumor has been surgically removed), this ovarian stimulation, because the expected benefits of fertility preservation far outweigh the risks. However, everyone agrees that it would be more comfortable to be able to offer vitrification of oocytes and/or embryos using ovarian stimulation without increasing estrogen levels.

Therefore, the limitation of serum estradiol concentrations during stimulation represents an important issue. To this end, stimulation protocols combining aromatase inhibitors have been proposed. Inhibition of the P450 aromatase enzyme in the granulosa cells of stimulated follicles prevents the conversion of androgens to estrogens. However, the teratogenic risk of these molecules, although discussed, limits their use in the indication of COS. Recently, a new "natos" protocol was proposed to stimulate the ovaries while maintaining physiological estradiolaemia, without using aromatase inhibitors. Thus, the administration of high doses of Gonadotropin Releasing Hormone (GnRH) antagonists (3 to 6 injections of 0.25 mg/day) from the beginning of COS, would allow a strong Luteinizing Hormone (LH) deprivation, thus limiting the production of androgens according to the 2 cells - 2 gonadotropins theory. In the absence of a precursor, estradiolemia remains at physiological ranges during the total duration of COS. However, the relative heaviness of a protocol combining up to 8 daily injections limits its use in young women who are candidates for fertility preservation.

Investigators therefore propose to evaluate the efficacy and tolerance of a new natos-like COS protocol based on the administration of a long-acting GnRH antagonist, degarelix. This drug is currently off-label for women.

The expected duration of the research is 14 months and participation will be 2 months.

After signature of the consent, during the first visit (oncofertility counseling), the the research (consultations and examinations) will be carried out within the Antoine Béclère hospital. All visits and examinations performed are part of routine care, except for the injection(s) of degarelix which belongs to the research.

Inclusion visit During the oncofertility consultation, the physician will make sure that the patient can be included in the research. Once the consent has been signed, the doctor will schedule the following visits based on the biological results obtained as part of the usual care.

Research follow-up visits

Stimulation: between the day of oncofertility counseling and the following 7 days, the doctor will check that patients are in the early follicular phase of the cycle, Degarelix injection: 1 injection, under the skin (possibly renewable after 5-7 days if the serum LH is ≥2 IU / L and / or the estradiol is ≥400 pg / mL), Concomitant initiation of ovarian stimulation by administration of recombinant FSH - Follitropin alfa (usual care). The injections will be given by the patient or a nurse at home, between 7pm and 10pm.

Stimulation follow-up visit #1 :

After 5 days of ovarian stimulation, transvaginal pelvic ultrasound (counting of ovarian follicles and measurement of their diameters) and blood sampling for serum hormone assays (estradiol, LH, progesterone) will be performed as part of the usual care.

Stimulation follow-up visits #2 and #3 Visits #2 and #3: transvaginal pelvic ultrasound (counting of ovarian follicles and measurement of their diameters) and a blood test for serum hormone assays (estradiol, LH, progesterone) will be required to monitor the response to stimulation, as part of routine care.

Visits are repeated until 4 follicles 16 to 20 mm in diameter are obtained, which is the criterion for ovulation trigger using 1 injection of Human Chorionic Gonadotropin (hCG) (Ovitrelle 250 mcg, SC) (usual care). Thus visits #2 and #3 are systematic. One or two additional visits with the same examinations may sometimes be necessary if the trigger criteria are not met.

Thirty-six hours after Human Chorionic Gonadotropin (hCG) , oocyte retrieval will be performed.

Visit on the day of the oocyte retrieval:

Patients will have a venous blood sample for serum hormone assays (estradiol, LH, progesterone) as part of the usual care.

Oocyte collection will be scheduled, and those which are mature will then be frozen (by vitrification) or fertilized in vitro in case of embryo freezing.

Visit following egg retrieval:

A blood test for serum hormone assays (estradiol, LH, progesterone) will be performed 3-4 days after oocyte retrieval.

End of research visit Participants will be contacted by phone 2 months after the injection of degarelix (Firmagon®) to make sure they are fine.

Efficacy and Tolerance of an Ovarian Stimulation Protocol Combining Follicle Stimulating Hormone (FSH) and Degarelix Acetate in Female Candidates for Fertility Preservation Before Chemotherapy for Breast Cancer

Efficacy and Tolerance of an Ovarian Stimulation Protocol Combining FSH and Degarelix Acetate in Female Candidates for Fertility Preservation Before Chemotherapy for Breast Cancer

Success of the procedure if at least 4 follicles 16 to 20 mm in diameter are obtained on the day of ovulation trigger (36 hours before oocyte collection) with estradiolemia \<500 pg / mL

Percentage of women with hyperestradiolemia during controlled ovarian stimulation (COS)

Outcome of ovarian stimulation evaluated by the number of oocytes collected, and the number of mature oocytes vitrified

Description : Serious side effects associated with treatment with degarelix (MedDRA coding)

Assistance Publique - Hôpitaux de Paris

Symptoms and General Pathology

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

Other Dietary Supplements

Carnitine

The controlled ovarian stimulation procedure in all the study participate will be same by using a flexible regimen of GnRH antagonist with E2 priming. In the experimental group, the women will receive 3 tablet of L-carnitine daily (L-carnitine® tablet 1000 mg, Karen Pharmaceutical Company, Iran) from day 2 of the previous menstrual cycle until pregnancy test day.

The controlled ovarian stimulation procedure in all the study participate will be same by using a flexible regimen of GnRH antagonist with E2 priming. The patients in the control group will receive 3 placebo tablets in similar way for 8 weeks.

Prescription 3mg l-carnitine (L-carnitine® tablet 1000 mg, Karen Pharmaceutical Company, Iran) daily from day 2 of the previous menstrual cycle until pregnancy test day (approximately 8 weeks).

L-carnitine 1000 Mg

Maryam Hafezi, MD.

The aim of this study was to evaluate the effect of oral L-carnitine supplementation during controlled ovarian stimulation (COS) in patients with polycystic ovary syndrome (PCOS) in a double-blind randomized clinical trial. The eligible patients with PCOS diagnosis (on the basis of Rotterdam criteria) who referred to Royan Research Institute for IVF / ICSI treatment cycles will be evaluated.

The study protocol was approved by the Institutional Review Board and Ethics Committee of Royan institute. Prior to the onset of ovarian stimulation, patients will be allocated randomly into two groups according to block randomization method. The methodologist will give the doctor a code according to the randomization list, which corresponds to the code on the drug's box, and the drug box will be delivered to the patient. The COS procedure in all the study participate will be same by using a flexible regimen of GnRH antagonist with E2 priming. In the experimental group, the women received 3 tablet of L-carnitine daily (L-carnitine® tablet 1000 mg, Karen Pharmaceutical Company, Iran) from day 2 of the previous menstrual cycle until pregnancy test day. The patients in control group will receive 3 placebo tablets for 8 weeks. All the placebo tablets were produced by Karen company (Tehran, Iran), which is approved by the Food and Drug Administration of Iran. The appearance of the placebo was indistinguishable in color, shape, size, and smell from L-carnitine tablets. Ovarian stimulation will start with a maximum dose of 150 units of rFSH (Gonal -F: Serono Laboratories Ltd, Geneva, Switzerlan), from the second or third day of the spontaneous or discontinued progesterone menstrual cycle and the monitoring transvaginal ultrasound was performed and then if the follicle is observed, start with 13 injections of GnRH antagonist (Cetrotide®, 0.25 mg cetrorelix acetate, Serono, Inc) and will be continued until the oocyte triggering day. From the seventh day of the cycle, the dose of rFSH will be determined according to the rate of ovarian response by vaginal ultrasonography two days in advance. If you see at least two follicles 18 mm in size or more, the final stimulation of oocyte maturation will be done and 34- 36 hour after that the ovum pickup will be conducted. Subsequently ICSI or IVF will be done with standard procedure. In the present study, the markers of insulin metabolism (fasting glucose and insulin) and lipid profiles (LDL, HDL, cholesterol and triglyceride) as well as body mass index and weight were measured at the baseline of the study (before starting L-carnitine supplementation) as well as 6 weeks later on the ovum pick up day.The outcome evaluators were also blinded to the random allocation process and type of treatment.The primary and secondary outcomes were compared between the two groups using appropriate statistical tests.

L-carnitine and placebo drugs can be identified only by special codes determined by a statistics specialist. The participant, care provider, investigator and outcome assessor are unaware of the type of study groups.

L-carnitine and COH in PCOS Women Undergoing IVF/ICSI Cycles

The Effect of Adding L-carnitine During Ovarian Stimulation With Antagonistic Protocol in Patients With Polycystic Ovarian Syndrome on the Outcome of IVF / ICSI Cycle: A Double Blind Randomized Clinical Trial

Oocyte maturity was defined as the ratio of metaphase II (MII) oocytes to the number of collected oocytes in thepatients undergoing with ICSI.

Fertilization rate was defined as the ratio of normal fertilized oocytes (2PNs) to the number of oocytes used for fertilization.

Embryo quality were determined according to the number of cells, the amount of fragmentation, the variation in cell size and overall symmetry (perfect, moderately asymmetric, and severely asymmetric in size and shape of the cells at Day 2 or Day 3 after oocyte retrieval:

Excellent (Day 3: 6-8 even size blastomeres with ≤10% fragmentation), Good (Day 3: 6-8 even or uneven size blastomeres with 10%-20% fragmentation), Poor (Uneven and few blastomeres with \>20% fragmentation)

The number of gestational sacs observed at trans-vaginal ultrasonography screening at 6 weeks of pregnancy divided by the number of embryos transferred.

Clinical pregnancy rate per transfer as defined by the presence of a gestational sac with heart beat on ultrasound at 6-8 weeks of gestation

Ongoing pregnancy was defined as a pregnancy documented by ultrasound at 20 gestational weeks that showed the presence of fetal heartbeat.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Efficacy and Tolerance of an Ovarian Stimulation Protocol Combining Follicle Stimulating Hormone (FSH) and Degarelix Acetate in Female Candidates for Fertility Preservation Before Chemotherapy for Breast Cancer	NCT03947151	Invasive Ductal...	Degarelix injec...	18 Years - 40 Years	Assistance Publique - Hôpitaux de Paris
L-carnitine and COH in PCOS Women Undergoing IVF/ICSI Cycles	NCT04672720	Polycystic Ovar...	L-carnitine 100...	20 Years - 37 Years	Royan Institute

Spots Global Cancer Trial Database for controlled ovarian stimulation