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Triptorelin Pamoate

Ganirelix

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Hormone Antagonists

Arvekap 0.1mg (Triptorelin, Ipsen, France)

Ganirelix 0.25mg (Orgalutran, Organon, The Netherlands)

Tryfon Lainas, PhD

The purpose of this study is to compare pregnancy rates and the occurrence of OHSS in PCOS patients who were treated with GnRH agonist and GnRH antagonist protocols ovarian stimulation during an IVF cycle. Our hypothesis is that the GnRH antagonist protocol reduces the occurrence and severity of OHSS compared to the GnRH agonist protocol.

Women with polycystic ovarian syndrome (PCOS) represent a group of patients at high risk of developing ovarian hyperstimulation syndrome (OHSS), an iatrogenic complication of ovarian stimulation during IVF treatment. In contrast to mild OHSS, severe OHSS is a life-threatening complication, characterized by massive ovarian enlargement, ascites, pleural effusion, oliguria, haemoconcentration and thromboembolic phenomena. Currently, no curative therapy for OHSS is available and thus prevention is considered the most effective "treatment". Several measures have been adopted to reduce the occurrence of the syndrome, the most effective being cycle cancellation and withholding of human chorionic gonadotropin (hCG), which seems to be the most critical factor for the development of OHSS.

COMPARISON: This study aims to compare the development and severity of OHSS, as well as ongoing pregnancy rates in PCOS patients who received a flexible GnRH antagonist (Ganirelix) protocol vs a long GnRH agonist (Arvekap) protocol of ovarian stimulation.

Comparison Between GnRH Agonist and GnRH Antagonist Protocols of Ovarian Stimulation in PCOS Patients

Randomized Controlled Trial Comparing the Effect of GnRH Agonist and Antagonist Ovarian Stimulation Protocols in PCOS Patients

Eugonia

Infertility

Hypoglycemic Agents

Metformin

Patients receiving metformin pretreatment and co-administration

Metformin pre-treatment and co-administration

Placebo pre-treatment and co-administration

Placebo administration

Stefano Palomba

Fulvio Zullo

The use of metformin pre-treatment and co-administration was recently proposed in infertile women affected by polycystic ovary syndrome (PCOS) treated with gonadotropins.

Data from meta-analyses showed that metformin administration significantly reduced the stimulation length and the total dose of gonadotropins used in PCOS women undergoing gonadotropins stimulation for non in-vitro fertilization (IVF) cycles. On the other hand, in IVF cycles metformin was demonstrated to significantly reduce the ovarian hyperstimulation syndrome (OHSS) rate in infertile patients with PCOS treated with gonadotropins.

The metformin regulating effect on the ovarian response was also observed in a randomized controlled trial (RCT) on young non-obese insulin-resistant women with PCOS receiving gonadotropins for mono-ovulation induction. In particular, metformin increased the mono-ovulatory cycles, the duration of stimulation and the amount of gonadotropins used, while it reduced the number of dominant follicles and the estradiol (E2) levels.

The aim of the present study was to evaluate the effect of metformin administration in high responder PCOS patients undergoing gonadotropins ovarian stimulation for IVF cycles.

Infertile young non-obese insulin-resistant patients with PCOS who had a background of the first IVF treatment cycle cancelled because of high risk for OHSS will be enrolled and randomized in two treatment arms.

In their second IVF attempt, the experimental group will receive metformin (500 mg, 3 times daily) pre-treatment for two weeks and co-administration during gonadotropins ovarian stimulation; the control group will be treated with placebo (2 cps daily) pre-treatment and co-administration by using the same schedule of the experimental group. In all patients, ovarian stimulation will be carried out with a personalized step-down gonadotropin in association with a minidose flare-up GnRH agonist protocol.

Metformin in High Responder Polycystic Ovary Syndrome (PCOS) Patients Undergoing IVF Cycles

Metformin Addition to Gonadotropins Ovarian Stimulation in High Responder Patients With PCOS Undergoing In-vitro Fertilization

University Magna Graecia

Department of Obstetrics and Gynecology

Menotropins

In this prospective trial, women with PCOS (according to Rotterdam criteria) were randomized (80 patients) after GnRH analogue suppression to stimulation with HMG (n=38) or rFSH (n=42) using a low dose step up protocol in ICSI cycles.

Patients were randomized after GnRH analogue suppression to stimulation with HMG (n=38) or rFSH (n=42) using a low dose step up protocol in ICSI cycles.

rFSH

Figen A Turkcapar, MD

There have been some controversies regarding the use of preparations with LH activity in patients with polycystic ovary syndrome (PCOS) who have high endogenous LH activity. In this research we aimed to compare urinary menotrophin versus recombinant FSH (rFSH) with respect to the prevention of OHSS

Polycystic ovary syndrome was diagnosed according to the Rotterdam criteria. Patients older than 38 years or with serum FSH level ≥12mIU/ml and a history of ovarian surgery were excluded from the study. All of our patients were given combined oral contraceptive (Yasmin) prior to ovulation induction cycles. Leuprolide Acetate (Lucrin daily; Abbott, Istanbul) therapy was started in mid-luteal phase to induce pituitary down regulation, and was initiated at a dose of 1.0 mg SC daily until pituitary down-regulation was established. The leuprolide acetate dose was then reduced to 0.5 mg daily until the day of human chorionic gonadotropin (hCG) administration. After GnRH analogue suppression was achieved, the patients were randomized using block randomization (block of two) to stimulation with hMG (Menogon; Ferring Pharmaceuticals. Istanbul) or rFSH (Gonal-F; Serono Istanbul). Starting dose was 150IU for the first 3 days of stimulation, after which daily dosing was determined individually. Serial Estrodiol (E2) levels and two-dimensional follicle measurements by transvaginal ultrasonography (LOGIC 200 PRO, General Electric, Korea) were performed until at least two dominant follicles reached dimensions of 18 mm or greater in diameter. Human chorionic gonadotropin (Pregnyl, Organon, 10,000 IU- IM) was then administered, followed by transvaginal oocyte retrieval 36 hours later. The criteria of coasting in our institute were serum E2 \>3600 pg/ml and multiple intermediate follicle. During coasting period, gonadotropin was withheld, but leuprolide acetate was continued at 0.5mg/d. ICSI was performed for all the patients. Fertilization was assessed at 20h (±1h), and embryo quality was assessed at 28, 44, and 68h (±1h) after oocyte retrieval. A top- quality embryo was defined as four to five cells on day 2, seven or more cells on day 3, and no multinucleation. Vaginal progesterone gel 90 mg/day 8% (Crinone;Serono) for luteal support was given from the oocyte retrieval until the clinical pregnancy (9-10 weeks of gestation) or negative serum βhCG test (13-15 days after embryo transfer).

hMG or Recombinant FSH on OHSS Prevention in PCOS Patients Undergoing IVF

Influence of Ovarian Stimulation With hMG or Recombinant FSH on OHSS Prevention in PCOS Patients Undergoing IVF

Zekai Tahir Burak Women's Health Research and Education Hospital

Women receive 20 mg of Degarelix on the first day of menstrual cycle followed by a fixed dose of 225 IU of recombinant FSH on the second day until the day of ovulation triggering

GnRH antagonist depot Degarelix

Mauro Schimberni, MD

PCOS is a common endocrinopathy affecting 5-10% of women in their reproductive age characterized by hyperandrogenism, chronic anovulation and polycystic ovaries. This syndrome is a serious problem in IVF since there is a high risk of developing ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation with gonadotropins. The introduction of GnRH antagonist in IVF has reduced the incidence of severe OHSS, still maintaining a good ovarian response and pregnancy rate. Recently, a long acting GnRH antagonist, Degarelix, was introduced for prostatic cancer treatment. Furthermore a recent paper reported its use also for the induction of multiple follicular growth in a program of oocyte donation. The aim of this study is to evaluate the feasibility of GnRH antagonist depot use in a protocol of controlled ovarian hyperstimulation in PCOS women at risk of developing OHSS in IVF cycles.

Long Acting GnRH Antagonist in PCOS Women Undergoing IVF

The Use of a Long Acting GnRH Antagonist (Degarelix) in Controlled Ovarian Hyperstimulation in PCOS Women at a Risk to Developing OHSS Undergoing IVF : a Pilot Study

Bioroma

PCOS women with AMH level (≥ 7 ng/ml) who underwent LOD in the preceding 3 months prior to IVF/ICSI

PCOS women with AMH level (≥ 7 ng/ml) who did not undergo LOD in the preceding 3 months prior to IVF/ICSI

Women underwent LOD in the preceding 3 months prior to IVF/ICSI

Mohamed S Abdelhafez, Dr

Alaa Wageh, Dr

Waleed El-refaie, Dr

Maher Shams, Dr

To evaluate the effect of performing laparoscopic ovarian drilling (LOD) before proceeding to in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) on the cycle outcomes in polycystic ovarian syndrome (PCOS) patients with high antimullerian hormone (AMH) levels

Retrospective case-control study of PCOS women with high serum AMH level (≥ 7 ng/ml) who were subjected IVF/ICSI. Women underwent LOD in the preceding 3 months prior to IVF/ICSI (study group) will be compared with a control group of women who did not underwent LOD (control group)

LOD Before IVF/ICSI in PCOS Patients With High AMH

Laparoscopic Ovarian Drilling Before IVF/ICSI in Polycystic Ovarian Syndrome Patients With High Antimullarian Hormone

Number of collected oocytes during oocyte retrieval

Calculated for each woman by dividing the number of mature oocytes (MII oocytes) by the total number of oocytes retrieved

Calculated for each couple by dividing the number of fertilized oocytes by the number of injected (or inseminated) oocytes

Number of clinical pregnancies (defined as presence of at least one intrauterine gestational sac with fetal pole and cardiac activity on TVS scan at 4-6 weeks after the ET) divided by the number of ET procedures

Number of gestational sacs on TVS scan at 4-6 weeks after ET divided by the number of transferred embryos

Incidence of OHSS within 9 days of final triggering of oocyte maturation

Mansoura University

Principal Investigator

Leuprolide

Cetrorelix

Contraceptives, Oral

Chorionic Gonadotropin

Day 1 of 1st menstruation: OC for 18-21 days (Microdiol ®) + Metformin (Dianben ®) 850 x 2/day if: BMI\>30, HOMA \>3.8, G/I ratio \<4.5

Day 18-24 of cycle: Leuprorelin (Procrin ®) 0.1 s.c. for 14-21 days

Day 1 of 2nd menstruation (=Day 1 COH cycle): Hormonal profile (FSH, LH, E2, Pg, T, SHBG), Ultrasonography to exclude cyst \>10 mm

Day 2of COH cycle: rFSH (Gonal F ®) 150 IU/day for 4 days; Leuprorelin (Procrin ®) 0.1 s.c. (and following days)

Day 7 of COH (and following): Measure FSH, LH, E2, Pg + Ultrasound

Day before HCG: stop rFSH

Day HCG: measure FSH, LH, E2, Pg, administer 250 mcg Choriogonadotropin-alfa ( Ovitrelle®)

Day of pick-up: Follicular fluid from 1st follicle to be centrifuged and stored at -20°C

Day 7 after pick-up: ultrasound, patient evaluation.

Day 14 after pick-up: HCG in blood

Day 28 after pick-up: Ultrasound to visualize heart beat if pregnancy test positive

(OC= oral contraceptive; COH= Controlled Ovarian Hyperstimulation)

Controlled ovarian hyperstimulation for IVF with a long agonist protocol

Day 1 of pre COH-cycle: OC for 18-21 days (Microdiol ®) + Metformin (Dianben ®) 850 x 2/day if: BMI\>30, HOMA \>3.8, G/I ratio \<4.5

Day 3 of free-pill interval: Hormonal profile (FSH, LH, E2, Pg, T, SHBG), Ultrasonography to exclude cyst \>10 mm

Day 5 of free-pill interval (=Day 1 COH cycle): Cetrorelix acetate (Cetrotide®) 0.25 mg s.c. + rFSH (Gonal F ®) 150 IU/day (and following days)

Day 3-4-10 of COH cycle: measure FSH, LH, E2, Pg + ECO

Day before HCG: stop rFSH + cetrorelix

Day HCG: measure FSH, LH, E2, Pg, administer 250 mcg Choriogonadotropin-alfa ( Ovitrelle®)

Day of pick-up: Follicular fluid from 1st follicle to be centrifuged and stored at -20°C

Day 7 after pick-up: ultrasound, patient evaluation.

Day 14 after pick-up: HCG in blood

Day 28 after pick-up: Ultrasound to visualize heart beat if pregnancy test positive (OC= oral contraceptive; COH= Controlled Ovarian Hyperstimulation)

Controlled ovarian hyperstimulation for IVF with an antagonist protocol

Fulvia Mancini, M.D. PhD

The aim of this study is to compare two different IVF-stimulation protocols in patients affected by PCOS: the use of a Gonadotropin-releasing hormone (GnRH) - antagonist starting on day 1 of controlled ovarian hyperstimulation (COH) versus a standard long agonist protocol; in order to assess whether it affects the number and quality of Metaphase II (MII) oocytes while reducing the risk of hyperstimulation. Since PCOS patients are also likely to be insulin resistant we also aim to evaluate how metformin affects tha IVF stimulation outcome.

Hejinen et al (1) recently conducted a meta-analysis to compare outcomes of conventional IVF in women presenting with polycystic ovary syndrome (PCOS) and non-PCOS patients. They compared nine RCTs reporting data on 458 PCOS patients (793 cycles) and 694 matched controls (1116 cycles) and concluded that in PCOS there is an increased cancellation rate, but more oocytes retrieved per pick-up and a lower fertilization rate. Overall, PCOS and control patients achieved similar pregnancy and live birth rates per cycle. The incidence of ovarian hyperstimulation syndrome (OHSS) after oocyte retrieval was rarely reported.

Our results are in accordance with this meta-analysis. Therefore, if the pregnancy and abortion rates in PCOS and controls do not differ, the main problem when dealing with PCOS in IVF is OHSS. This condition can be approached by using an antagonist instead of an agonist, by changing the kind of ovulation trigger and by co-treating patients with metformin.

* One of the currently debatable issues regarding the use of GnRH antagonists refers to the timing of GnRH antagonist initiation. A fixed protocol starting antagonist arbitrarily on Day 6 of stimulation has been used in all introductory comparative trials employing a daily antagonist administration (2). Following these trials, a flexible antagonist initiation by a follicle of 14-15 mm has been evaluated. Currently, initiation of antagonist in the early follicular phase in PCOS patients has been performed by Lainas and coll. (3) who treated patients with PCOS either with a long GnRH agonist scheme or a fixed day-1 GnRH antagonist protocol and concluded that initiation of GnRH antagonist concomitantly with recombinant FSH on day 1 is associated with an earlier follicular growth and a different hormonal environment during the follicular phase when compared with the long agonist protocol. This may lead to a reduction in the incidence of OHSS.
* Over the past 15 years, it has become increasingly recognized that insulin resistance is central to the pathogenesis of the PCOS (4). Metformin, a biguanide insulin-lowering agent, has been extensively investigated in the management of PCOS. Two recent systematic reviews (5, 6) demonstrated that metformin improves reproductive function of some women with PCOS. Metformin also appeared to improve the outcomes of ovulation induction therapies when combined with clomiphene and gonadotrophin. Tang et al. recently studied PCOS overweight patients undergoing IVF to whom they administered 850 mg bid or placebo 28 days prior to the stimulation (7). They concluded that short-term co-treatment with metformin for patients with PCOS undergoing IVF/ICSI cycles does not improve the response to stimulation but significantly improves the pregnancy outcome and reduces the risk of OHSS.

The aim of this study is to verify if using an antagonist the number and quality of MII oocytes is equal compared to a standard long agonist protocol while reducing the risk of hyperstimulation.

Outcome measures:

Primary endpoints:

* Oocytes MII Secondary endpoints
* Fertilization rates
* Pregnancy rates
* Miscarriage rates
* Incidence of OHSS

Polycystic Ovary Syndrome (PCOS) and In Vitro Fertilization (IVF): A Comparison Between Standard Long Protocol Versus an Antagonist Protocol Starting on Day 1

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Comparison Between GnRH Agonist and GnRH Antagonist Protocols of Ovarian Stimulation in PCOS Patients	NCT00417144	Polycystic Ovar... Ovarian Hyperst...	Arvekap 0.1mg (... Ganirelix 0.25m...	18 Years - 50 Years	Eugonia
Metformin in High Responder Polycystic Ovary Syndrome (PCOS) Patients Undergoing IVF Cycles	NCT01233206	Infertility Polycystic Ovar...	Metformin Placebo adminis...	18 Years - 35 Years	University Magna Graecia
hMG or Recombinant FSH on OHSS Prevention in PCOS Patients Undergoing IVF	NCT01365936	Polycystic Ovar...	HMG rFSH	20 Years - 38 Years	Zekai Tahir Burak Women's Health Research and Education Hospital
Metformin in High Responder Polycystic Ovary Syndrome (PCOS) Patients Undergoing IVF Cycles	NCT01233206	Infertility Polycystic Ovar...	Metformin Placebo adminis...	18 Years - 35 Years	University Magna Graecia
Long Acting GnRH Antagonist in PCOS Women Undergoing IVF	NCT02084940	Polycystic Ovar... Ovarian Hyperst... Invitro Fertili...	GnRH antagonist...	23 Years - 37 Years	Bioroma
Comparison Between GnRH Agonist and GnRH Antagonist Protocols of Ovarian Stimulation in PCOS Patients	NCT00417144	Polycystic Ovar... Ovarian Hyperst...	Arvekap 0.1mg (... Ganirelix 0.25m...	18 Years - 50 Years	Eugonia
Long Acting GnRH Antagonist in PCOS Women Undergoing IVF	NCT02084940	Polycystic Ovar... Ovarian Hyperst... Invitro Fertili...	GnRH antagonist...	23 Years - 37 Years	Bioroma
LOD Before IVF/ICSI in PCOS Patients With High AMH	NCT03358199	Infertility Polycystic Ovar...	LOD	18 Years - 35 Years	Mansoura University
Polycystic Ovary Syndrome (PCOS) and In Vitro Fertilization (IVF): A Comparison Between Standard Long Protocol Versus an Antagonist Protocol Starting on Day 1	NCT00883766	Polycystic Ovar... In Vitro Fertil...	Controlled ovar... Controlled ovar...	18 Years - 37 Years	Institut Universitari Dexeus

Spots Global Cancer Trial Database for ohss

Every month we try and update this database with for ohss 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 ohss

Every month we try and update this database with for ohss 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 ohss 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.