"Stair Step Study"
Ключови думи
Резюме
Описание
OBJECTIVES
Primary objective:
To demonstrate whether withholding progesterone induced endometrial shedding prior to ovulation induction improves the ongoing pregnancy rate per cycle compared to not withholding progesterone treatment and to demonstrate its impact on the time to pregnancy.
Secondary objectives:
To elucidate the impact of the two study protocols on time to ovulation, endometrial thickness, multiple follicle growth, multiple pregnancy and the incidence of treatment failure. Furthermore, in accordance to the proposed areas of focus addressed by feasibility studies [Bowen et al (2009)], the number of eligible patients, the number of protocol violations and the number of drop-outs will be recorded.
STUDY DESIGN
Prospective multicenter randomized controlled study. The participating centers are:
- Radboud UMC, Nijmegen
- Canisius Wilhelmina Ziekenhuis (CWZ), Nijmegen
- Gelderse Vallei, Ede
Patients will be randomly allocated to receive one of the following treatment protocols:
- Standard group: medroxyprogesterone acetate (Provera®) 10 mg for 10 days prior to starting ovulation induction with CC and in between anovulatory cycles.
- Stair Step group: no Provera® prior to ovulation induction with CC, nor in between anovulatory cycles.
Standard group The standard group will receive our standard care. Provera® will be administered for 10 days (after a negative pregnancy test) to induce an endometrial whitdrawal bleeding. Menses may be expected as early as 3 days after the last pill. Prior to each treatment cycle, an ultrasound will be performed on cycle day 3 to check up on the presence of cysts after which CC 50 mg is administered for 5 days. Follicle growth will be monitored by ultrasound, starting from cycle day (CD) 11. If there is no response (defined as no follicle ≥ 14 mm) on CD 20, Provera® will be administered for 10 days. The CC dosage will be increased in the next cycle. Three days after the start of the next menses, patients will receive CC 100 mg for 5 days with follicle growth monitoring starting again from CD 11. Anovulatory patients (no follicle ≥ 14 mm) on CD 20 will receive Provera® for 10 days. Three days after the start of menses the CC dose will be increased to 150 mg and will be administered for 5 days with ultrasounds starting from CD 11-20.
Stair Step group The stair-step group will receive the following treatment: after performing an ultrasound to check for the presence of cysts or any other abnormalities and a negative pregnancy test, patients will be given CC 50 mg for 5 days. Ultrasounds will be performed on days 11-14. When there is no response on CD 14 (no follicle ≥ 14 mm), the dose of CC is immediately increased to 100 mg CC for 5 days and an ultrasound is performed 1 week following the last ultrasound. If there is no response, 150 mg CC is initiated immediately for 5 days and the ultrasound is repeated 1 week after the previous ultrasound.
In both arms, ovulation is confirmed by evidence of a preovulatory follicle followed by menses with onset at the expected time (cycle length of 25-35 days) or by pregnancy.The CC dose can be adjusted in case of a high response. Treatment failure is defined as failure to ovulate following CC 150 mg. Patients who conceive will receive an ultrasound examination at 8 weeks of gestation to confirm an ongoing pregnancy. Following this last scan the study period for the given patient will be completed. All patients will undergo a maximum of 3 treatment cycles as part of this protocol.
Дати
| Последна проверка: | 07/31/2017 |
| Първо изпратено: | 08/08/2017 |
| Очаквано записване подадено: | 10/11/2017 |
| Първо публикувано: | 10/12/2017 |
| Изпратена последна актуализация: | 06/03/2018 |
| Последна актуализация публикувана: | 06/05/2018 |
| Действителна начална дата на проучването: | 06/20/2016 |
| Приблизителна дата на първично завършване: | 11/29/2017 |
| Очаквана дата на завършване на проучването: | 05/30/2018 |
Състояние или заболяване
Интервенция / лечение
Drug: Standard group
Other: Stair Step group
Фаза
Групи за ръце
| Arm | Интервенция / лечение |
|---|---|
| Active Comparator: Standard group Intervention:Medroxyprogesterone acetate (Provera) 10 mg daily for 10 days will be used prior to starting ovulation induction with clomiphene citrate (CC) and between anovulatory cycles. On cycle day (CD) 3 CC 50 mg is administered daily for 5 days. Follicle growth will be monitored by ultrasound, starting from CD11. Anovulatory patients (defined as no follicle ≥ 14 mm) on CD20, will receive Provera 10mg daily for 10 days. The CC dosage will be increased in the next cycle. On CD3 patients will receive CC 100 mg daily for 5 days with ultrasounds performed from CD11 onwards. Anovulatory patients will receive Provera 10mg daily for 10 days. In the next cycle the CC dose will be increased to 150 mg, starting from CD3, daily for 5 days with ultrasounds starting from CD11-20. | Drug: Standard group Patients in the standard arm will receive Medroxyprogesterone Acetate 10mg daily for 10 days prior to the first ovulation induction cycle and in between anovulatory cycles. |
| Experimental: Stair Step group Intervention: Stair step protocol without medroxyprogesterone acetate 10 mg prior to ovulation induction with clomiphene citrate (CC), nor in between anovulatory cycles. After performing an ultrasound to check for the presence of cysts or any other abnormalities and a negative pregnancy test, patients will receive CC 50 mg daily for 5 days. Ultrasounds will be performed on CD11-14. If there is no response on CD14 (no follicle ≥ 14 mm), the dose of CC is immediately increased to 100 mg CC daily for 5 days and an ultrasound is performed 1 week following the last ultrasound. If there is no response, 150 mg CC daily is initiated immediately for 5 days and the ultrasound is repeated 1 week after the previous ultrasound. | Other: Stair Step group No administration of Medroxyprogesterone Acetate prior to each cycle. Stair step method: rapidly increasing the dose of clomiphene citrate in case of no follicular response |
Критерии за допустимост
| Възрасти, отговарящи на условията за проучване | 18 Years Да се 18 Years |
| Полове, допустими за проучване | Female |
| Приема здрави доброволци | Да |
| Критерии | Inclusion Criteria: - WHO classification category 2 PCOS or non-PCOS - Age between 18 - 41 years - Patent Fallopian tubes, proven by hysterosalpingography (HSG), a negative Chlamydia antibody titre (CAT) or diagnostic laparoscopy combined with tubal testing (DLS and TT), depending on the local protocol. - BMI < 40 kg/m2 Exclusion Criteria: - BMI > 40 kg/m2 - Previous unsuccessful ovulation induction cycles with CC - Double-sided tubal pathology - Presence of ovarian cysts on ultrasound - Moderate - severe male infertility (TMSC < 3 million) - Grade III/IV endometriosis - Thrombosis - Severe liver disease |
Резултат
Първични изходни мерки
1. Ongoing pregnancy rate per cycle [in case of pregnancy: 8 weeks after the start of each cycle, (maximum of 3 cycles, duration of 1 cycle: 28-35 days)]
2. Time to pregnancy [duration of 1 cycle: 28-35 days, a maximum of 3 cycles will be performed (pregnancy test will be performed at the end of the cycle if there is no menstruation)]
Вторични изходни мерки
1. Time to ovulation [3 cycles of 28-35 days, calculated as 14 days before the start of menstruation or 14 days before a positive pregnancy test]
2. Endometrial thickness on the last day of ultrasonography [maximum of 3 cycles (each 28-35 days)]
3. The incidence of multiple follicle growth on the last day of ultrasonography [maximum of 3 cycles (each 28-35 days)]
4. The incidence of multiple pregnancy [in case of pregnancy: 8 weeks after the start of a treatment cycle (maximum of 3 cycles; each 28-35 days)]
5. The incidence of treatment failure [maximum of 3 cycles (each 28-35 days)]
6. The number of eligible patients [Inclusion 16 months, follow-up 3 months.]
7. The number of protocol violations [duration: maximum of 3 cycles (each 28-35 days)]
