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We speculate that the use of combined oral contraceptives may be a possible solution to promote the management of retained pregnancy products versus expectant management. By withdrawing the pill, the endometrium is expected to shed in a synchronized fashion (estrogen and progestin withdrawal bleeding and may also shed the retained products of conception and avoid a surgical procedure with its related potential complications.
Miscarriage is a common event in general gynaecological practice, and is an age-dependent outcome. It is estimated -that approximately 20 percent of clinically recognized pregnancies will result in a miscarriage, and the prevalence is much higher if preclinical pregnancies are included as well .Failure to pass the contents of the pregnancy is reported in 15% of patients going through a spontaneous 1st trimester miscarriage and a similar rate in patients going through an induced medical abortion after a spontaneous pregnancy loss (miscarriage) and planned pregnancy termination using PGE1 (MisWe speculate that the use of combined oral contraceptives may be a possible solution to promote the management of retained pregnancy products versus expectant management. The exposure to combined oral contraceptives is known to induce secretory and decidual changes in the endometrium .By withdrawing the pill, the endometrium is expected to shed in a synchronized fashion (estrogen and progestin withdrawal bleeding). We hypothesize that such withdrawal bleeding may also shed the retained products of conception and avoid a surgical procedure with its related potential complications. oprostol).
All patients diagnosed with RPOC according to the inclusion and exclusion criteria , will be asked to give their informed consent to take part in the study.
Once informed consent forms are signed, the patient will be randomized (using a randomization table handled by a 3rd party) into one of 2 groups:
We wish to emphasize that the current management in our ward is expectant management in the population eligible for this study.
All US scans will be performed by 2 qualified sonographers using a 7.5 MHz transvaginal transducer. 2D images in both sagittal and axial planes will be obtained. Sonographic features to be evaluated are: endometrial maximal thickness measured in the sagittal plan, presence or absence and size of an endometrial mass (3 dimensions) and grading of endometrial vascularity. Vascularity will be graded as type 0, 1, 2 or 3 defining no detectable, minimal (less then myometrium), moderate (nearly equal to myometrium) or marked vascularity respectively (4).
At enrollment the patient will be monitored and interviewed for the following variables :
Age, BMI, OB - GYN history, smoking status, Blood pressure, pulse rate,Temperature, blood count, HCG levels.
All patients will be invited to a follow up visit 3 weeks after randomization. The follow up visit will include again an ultrasound scan as described above.
In any case the patient is reporting a menstrual bleeding/ abdominal pain/ fever she will contact the 24hr available ER of the ward and will be evaluated for complications. After evaluation is completed the principal investigator will be contacted and the case will be discussed as for the need for additional measures and documented in the research file.
In the planned 4 week post randomization visit the following parameters will be monitored:
Blood pressure, pulse rate, Temperature, blood count, HCG levels as well as a review of any symptoms.
Following the interview a trans-vaginal scan will be performed in order to evaluate the cavity and any retained products existence and any presence of blood flow in case of a positive diagnosis.
In any case of retained products detected by ultrasound we will recommend a surgical hysteroscopy.
The oral contraceptives will be donated by DEXCEL LTD, ISRAEL to the hospital pharmacy, where it will be stored.
Brand name :FLAME containing 0.02 mg Ethinylestradiol and 0.075 mg Gestodene. Israeli authorities demand that a drug which is tested in a research will be provided to the participant without charging.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Oral contraceptives | Experimental | Oral contraceptive agent, given for free, for 3 weeks and a follow up visit a week after treatment withdrawal. |
|
| Expectant management | Sham Comparator | Expectant management for 3 weeks and a follow up visit a week later. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oral contraceptive | Drug | Daily oral contraceptive agent for 3 weeks (FLAME, containing 0.02 mg Ethinylestradiol and 0.075 mg Gestodene) |
|
| Measure | Description | Time Frame |
|---|---|---|
| persistent retained pregnancy products rate | rate | 4 weeks |
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Inclusion Criteria:
Exclusion Criteria:
Retaiend pregnancy products
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Anat Hershko Klement, MD | Contact | +972549170084 | anat.klement@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Anat Hershko Klement, MD | Meir Medical Center | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18825609 | Background | Chen BA, Creinin MD. Medical management of early pregnancy failure: efficacy. Semin Reprod Med. 2008 Sep;26(5):411-22. doi: 10.1055/s-0028-1087107. Epub 2008 Sep 29. | |
| 16225027 | Background | Griebel CP, Halvorsen J, Golemon TB, Day AA. Management of spontaneous abortion. Am Fam Physician. 2005 Oct 1;72(7):1243-50. |
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| ID | Term |
|---|---|
| D000027 | Abortion, Incomplete |
| ID | Term |
|---|---|
| D000022 | Abortion, Spontaneous |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D003276 | Contraceptives, Oral |
| D057832 | Watchful Waiting |
| ID | Term |
|---|---|
| D003271 | Contraceptive Agents, Female |
| D003270 | Contraceptive Agents |
| D012102 | Reproductive Control Agents |
| D045505 | Physiological Effects of Drugs |
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Once informed consent forms are signed, the patient will be randomized (using a randomization table handled by a 3rd party) into one of 2 groups:
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Data analysis will be performed according to group code .
| Expectant management | Other | No intervention and a follow up visit a wewk later |
|
| 12620443 | Background | Wang X, Chen C, Wang L, Chen D, Guang W, French J. Conception, early pregnancy loss, and time to clinical pregnancy: a population-based prospective study. Fertil Steril. 2003 Mar;79(3):577-84. doi: 10.1016/s0015-0282(02)04694-0. |
| 23674774 | Background | Sellmyer MA, Desser TS, Maturen KE, Jeffrey RB Jr, Kamaya A. Physiologic, histologic, and imaging features of retained products of conception. Radiographics. 2013 May;33(3):781-96. doi: 10.1148/rg.333125177. |
| 22232130 | Background | Casikar I, Lu C, Oates J, Bignardi T, Alhamdan D, Condous G. The use of power Doppler colour scoring to predict successful expectant management in women with an incomplete miscarriage. Hum Reprod. 2012 Mar;27(3):669-75. doi: 10.1093/humrep/der433. Epub 2012 Jan 9. |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D045506 | Therapeutic Uses |
| D017063 | Outcome Assessment, Health Care |
| D010043 | Outcome and Process Assessment, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |