UMIN-CTR Clinical Trial

Basic information
Public title	The efficacy of progestin primed ovarian stimulation (PPOS) during controlled ovarian stimulation(COS) for patients with endometriosis
Acronym	PPOS for patients with endometriosis
Scientific Title	The efficacy of progestin primed ovarian stimulation (PPOS) during controlled ovarian stimulation(COS) for patients with endometriosis
Scientific Title:Acronym	PPOS for patients with endometriosis
Region	Japan

Condition
Condition	infertility
Classification by specialty	Obsterics and gynecology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To investigate the clinical efficacy of PPOS during COS for patients with endometriosis
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Explanatory
Developmental phase	Phase IV

Assessment
Primary outcomes	The clinical pregnancy rate
Key secondary outcomes	1) total amount of FSH/HMG 2) number of growing follicle (<15mm) and mature follicle (<18mm), number of oocyte retrieved 3)the incidence of premature LH surge 4) fertilization rate, implantation rate 5) serum concentration of estradiol and progesterone (on the trigger day) 6) the incidence of OHSS 7) the viable embryo rate 8) ongoing pregnancy rate, early miscarriage rate, multiple pregnancy rate

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Active
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	In the study group, Dienogest (2mg/day 1mg tablet 2 times/day) is administered orally from the previous cycle. And trans-vaginal ultrasonography and serum hormone measurements are performed, to follow ultrasound confirmation of the absence of oocytes larger than 10 mm with serum E2 <70pg/ml. After that patients are administered human menopausal gonadotropin per day. The initiating dose of 150 IU per day is used for patients with an AMH level over 3.0 ng per ml or a high antral follicle count greater than 15, otherwise 225 IU HMG is used. Follicular monitoring start on day 8 or 9 after HMG administration. This monitoring is performed every 2 to 4 days using a transvaginal ultrasound examination to check the growing follicular size and the number of follicles. The HMG dose is increased by 75 IU when the growing speed of follicles is assessed as slow. When the main dominant follicle size is close to 20 mm in diameter, the final stage of oocyte maturation was triggered using a GnRH agonist or/and HCG. Patients receiving the final trigger (GnRH agonist /HCG) undergo transvaginal ultrasound-guided oocyte retrieval 35 to 37 hours after the trigger. All follicles with diameters larger than 10 mm are aspirated. All high quality embryos are cryopreserved for later transfer.
Interventions/Control_2	In the control group, patients were administered human menopausal gonadotropin and dydrogesterone per day from day 2 or 3 of the menstrual cycle onward, following ultrasound confirmation of the absence of oocytes larger than 10 mm. The initiating dose of 150 IU per day was used for patients with an AMH level over 3.0 ng per ml or a high antral follicle count greater than 15, otherwise 225 IU HMG was used. Follicular monitoring started on day 8 or 9 of the menstrual cycle. This monitoring was performed every 2 to 4 days using a transvaginal ultrasound examination to check the growing follicular size and the number of follicles.
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	43 years-old >
Gender	Female
Key inclusion criteria	Endometriosis-associated infertile women who undergo IVF-ET program. 1) woman who has endometrioid cyst (chocolate cyst) (cyst diameter smaller than 4cm) diagnosed by imaging. (The patient with endometrial cysts more than 4cm receive the reduction treatment with operation or medication before IVF-ET start.) 2) woman who give written informed consent before entry into this study.
Key exclusion criteria	1) Patients who documented cycles with no oocyte retrieved, any contraindications to ovarian stimulation treatment and 2) patients who has contraindication to DNG, GnRHa, EP, FSH, HMG, HCG 3) Patients who is judged to be inappropriate for this study by the doctor
Target sample size	80

Research contact person
Name of lead principal investigator	1st name Hirobumi Middle name Last name Kaimiya
Organization	Kamiya Ladies Clinic
Division name	Reproductive therapy
Zip code	0600003
Address	2-1, Nishi2, Kita3, Chuo-ku, Sapporo, Hokkaido, 0600003, Japan
TEL	011-231-2722
Email	kamiya@fine.ocn.ne.jp

Public contact
Name of contact person	1st name Nanako Middle name Last name Iwami
Organization	Kamiya Ladies Clinic
Division name	Reproductive therapy
Zip code	0600003
Address	2-1, Nishi2, Kita3, Chuo-ku, Sapporo, Hokkaido, 0600003, Japan
TEL	011-231-2722
Homepage URL
Email	nanakoiwami@gmail.com

Sponsor
Institute	Kamiya Ladies Clinic
Institute
Department

Funding Source
Organization	Kamiya Ladies Clinic
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	Kamiya Ladies Clinic
Address	2-1, Nishi2, Kita3, Chuo-ku, Sapporo, Hokkaido, 0600003, Japan
Tel	011-231-2722
Email	tozawa@kamiyaclinic.com

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2018 Year 02 Month 05 Day

Related information
URL releasing protocol
Publication of results	Partially published

Result
URL related to results and publications
Number of participants that the trial has enrolled	150
Results	During this study, no premature LH surge was detected. A smaller number of oocytes were retrieved in the dienogest(DNG) group than in the dydrogesterone(DYG) group (6.18 vs. 9.85); however, the rate of mature oocytes was significantly higher in the DNG group than in the DYG group (89.1% vs. 78.9%). The fertilization rate was comparable between two groups. Therefore, patients taking DNG for PPOS can continue endometriosis treatment and obtain good-quality embryos during COH.
Results date posted	2021 Year 02 Month 07 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results	2021 Year 03 Month 01 Day
Baseline Characteristics
Participant flow	For the DNG protocol, patients continued DNG and started the COH procedure at their individual discretion. Patients in the DYG group, who were not already receiving continuous hormonal treatment, started DYG simultaneously with ovarian stimulation on the second or third days of their menstrual cycles.
Adverse events	None
Outcome measures	The primary outcome was the fertilization rate among endometriosis patients. The secondary outcomes were the rate of oocyte maturation, the numbers of viable embryos, the clinical pregnancy rate, the ongoing pregnancy rate per frozen embryo transfer cycle, and the early miscarriage rate.
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Main results already published
Date of protocol fixation	2017 Year 11 Month 01 Day
Date of IRB	2018 Year 01 Month 31 Day
Anticipated trial start date	2018 Year 02 Month 05 Day
Last follow-up date	2021 Year 12 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded	2022 Year 12 Month 31 Day

Other
Other related information

Management information
Registered date	2018 Year 02 Month 02 Day
Last modified on	2022 Year 03 Month 02 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000035524