Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Modified Downregulation for Women With Adenomyosis of the Uterus Prior to Frozen-thawed Embryo Transfer. (MODA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03946722
Recruitment Status : Recruiting
First Posted : May 13, 2019
Last Update Posted : February 16, 2021
Sponsor:
Information provided by (Responsible Party):
University College, London

Brief Summary:

1 in 7 couples experience difficulty in conceiving. Many will require in vitro fertilization (IVF). IVF involves an initial period of downregulation to suppress the ovaries and prevent premature ovulation. Hormone injections are then used to stimulate a woman's ovaries to produce eggs which are removed by a minor operation. The harvested eggs are mixed with sperm to create embryos in the laboratory. These embryos are replaced in the womb a few days after they are created (fresh embryo transfer). Any remaining embryos are frozen such that they can be thawed and transferred at a later date (frozen thawed embryo transfer, FTET).

The investigators have previously shown that the presence of moderate or severe adenomyosis significantly reduces the chance of clinical pregnancy after embryo transfer. The purpose of this study is to examine whether it is possible to improve the chance of clinical pregnancy in these women by modifying the IVF protocol they undergo for FTET.

The hypothesis is that a prolonged downregulation regimen for women with adenomyosis would reduce the inflammatory reaction in the endometrium of these women and thus improve the chance of implantation after embryo transfer.

Consenting patients will be offered FTET. Those proceeding will be randomized to one of two protocols (A - standard protocol vs. B - prolonged downregulation protocol). Women will also be offered a questionnaire before and after IVF treatment to assess their adenomyosis symptoms .

The primary outcome of the study is clinical pregnancy defined as an intrauterine pregnancy with a visible heart beat older than 6 weeks gestation. Secondary outcomes include livebirth, pregnancy loss (biochemical pregnancy, miscarriage, ectopic pregnancy, stillbirth, termination of pregnancy), gestational age at delivery, birth weight, neonatal mortality, major congenital anomaly, serious medication reaction, number of frozen embryos available for transfer, number of days to achieve optimal endometrial thickness.


Condition or disease Intervention/treatment Phase
Adenomyosis Drug: GnRH analogue downregulation Other: Participant questionnaire Phase 4

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 162 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is a prospective, randomised controlled trial with two parallel arms. Frozen thawed embryo transfer takes approximately 6 weeks in a standard protocol, including a one week period of downregulation. Downregulation will be extended by five weeks in the modified protocol compared to the standard protocol. Participants will be followed up until the pregnancy outcome is determined, maximum 9 months after embryo transfer.
Masking: None (Open Label)
Masking Description: It will not be possible to perform blinding due to the difference in frequency of administration of medication between the two protocols, therefore an open label method will be used.
Primary Purpose: Treatment
Official Title: Modified Downregulation for Women With Adenomyosis of the Uterus Prior to Frozen-thawed Embryo Transfer.
Actual Study Start Date : August 17, 2020
Estimated Primary Completion Date : August 17, 2023
Estimated Study Completion Date : May 17, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pregnancy

Arm Intervention/treatment
Standard downregulation with GnRH analogue

Participants in this arm will be assigned to the routine IVF protocol currently being used in the investigators' IVF unit, as outlined below, with one week of downregulation. Downregulation is the suppression of the ovaries during an IVF cycle in order to perform controlled ovarian stimulation and prevent premature ovulation.

Start progesterone (Norethisterone 5mg twice daily orally) on day 14 of downregulation cycle and continue for 11 days. Start GnRH analogue (Buserelin 0.5ml subcutaneously once daily) on day 21 of downregulation cycle and reduce to 0.2ml on day 1 of bleed. Baseline scan on day 1 - 5 of bleed and start oestrogen (Progynova 2mg three times daily orally). Serial scanning from day 10 until endometrial thickness more than 8mm. Once endometrial thickness more than 8mm start progesterone (Cyclogest 400mg twice daily vaginally/rectally and Lubion 25mg twice daily subcutaneously) and proceed to embryo transfer on appropriate day for embryo age.

Drug: GnRH analogue downregulation

Downregulation is the suppression of the ovaries during an IVF cycle in order to perform controlled ovarian stimulation and prevent premature ovulation.

Participants will be exposed to one week of downregulation using a GnRH analogue in the standard downregulation arm and 6 weeks of downregulation using a GnRH analogue in the modified downregulation arm.


Other: Participant questionnaire
Participant will be offered the opportunity to complete an adenomyosis symptom assessment questionnaire at the start of their treatment, and again two months after completion of treatment.

Experimental: Prolonged downregulation with GnRH analogue

Participants in this arm will be exposed to an additional five weeks of downregulation using a GnRH analogue. Downregulation is the suppression of the ovaries during an IVF cycle in order to perform controlled ovarian stimulation and prevent premature ovulation.

Baseline scan on day 1-5 of bleed and administer GnRH analogue (Leuprorelin acetate 3.75 mg subcutaneously single injection). 28 days later administer second dose of GnRH analogue (Leuprorelin acetate 1.875 mg subcutaneously), and 21 days later start oestrogen (Progynova 2 mg three times daily orally). Serial scanning from day 10 of oestrogen until endometrial thickness more than 8mm. Once endometrial thickness more than 8mm start progesterone (Cyclogest 400mg twice daily vaginally/rectally and Lubion 25mg twice daily subcutaneously) and proceed to embryo transfer on appropriate day for embryo age.

Drug: GnRH analogue downregulation

Downregulation is the suppression of the ovaries during an IVF cycle in order to perform controlled ovarian stimulation and prevent premature ovulation.

Participants will be exposed to one week of downregulation using a GnRH analogue in the standard downregulation arm and 6 weeks of downregulation using a GnRH analogue in the modified downregulation arm.


Other: Participant questionnaire
Participant will be offered the opportunity to complete an adenomyosis symptom assessment questionnaire at the start of their treatment, and again two months after completion of treatment.




Primary Outcome Measures :
  1. Clinical pregnancy rate [ Time Frame: 6 weeks after embryo transfer ]
    Clinical pregnancy is defined as an intrauterine pregnancy with a visible heart beat older than 6 weeks gestation.


Secondary Outcome Measures :
  1. Livebirth [ Time Frame: 9 months after embryo transfer ]
    Pregnancy greater than 24 weeks

  2. Pregnancy loss [ Time Frame: 9 months after embryo transfer ]
    Includes biochemical pregnancy, miscarriage, ectopic pregnancy, stillbirth, termination of pregnancy

  3. Gestational age at delivery [ Time Frame: 9 months after embryo transfer ]
    Number of weeks at which infant is delivered

  4. Birthweight at delivery [ Time Frame: 9 months after embryo transfer ]
    Weight at time of delivery

  5. Neonatal mortality [ Time Frame: 9 months after embryo transfer ]
    The death of a baby before or during birth after 24 weeks of gestation

  6. Major cogenital anomaly [ Time Frame: 9 months after embryos transfer ]
    Major cogenital anomaly

  7. Serious medication reaction [ Time Frame: 9 months after embryo transfer ]
    Serious medication reaction

  8. Number of frozen embryos available for transfer [ Time Frame: Day of embryo transfer ]
    Number of frozen embryos available for transfer

  9. Number of days to achieve optimal endometrial thickness [ Time Frame: Start of endometrial preparation until day of embryo transfer ]
    Number of days to achieve optimal endometrial thickness

  10. Presence and severity of adenmyosis-related symptoms [ Time Frame: 2 months after embryo transfer ]
    Menorrhagia, dysmenorrhoea



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 42 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Adenomyosis of the uterus is a condition which affects women only.
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Couples who are undergoing a cycle of IVF/ICSI, where a cycle is defined as egg collection following ovarian stimulation.
  2. The female partner is ≥18 and < 42 years of age.
  3. The female partner has a BMI <30.
  4. Two out of three of the following criteria are met: AMH >5.4, FSH <8.9, antral follicle count >4.
  5. Moderate or severe adenomyosis of the uterus diagnosed on ultrasound scan.
  6. Both partners are willing and able to provide written informed consent.

Exclusion Criteria:

  1. Concurrent and/or recent involvement in other research that is likely to interfere with the intervention within the previous 3 months of study enrolment.
  2. Previous open or laparoscopic myomectomy
  3. Uterine fibroids (untreated FIGO Type 0-I-II and type III-IV fibroids > 3 cm)
  4. Use of GnRH analogues within previous 3 months.
  5. Severe male factor infertility (sperm count < 2 x 106/ml, use of surgically retrieved spermatozoa)
  6. Couples who in the opinion of the researcher by virtue of language or learning impairment would be unable to give fully informed consent to the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03946722


Contacts
Layout table for location contacts
Contact: Dimitrios Mavrelos, MRCOG MD 02034476550 dimitrios.mavrelos@nhs.net
Contact: Sania Latif, MRCOG sanialatif@nhs.net

Locations
Layout table for location information
United Kingdom
University College London Hospital Recruiting
London, United Kingdom, NW1 2BU
Contact: Dimitrios Mavrelos, MRCOG MD       dimitrios.mavrelos@nhs.net   
Contact: Sania Latif, MRCOG       sanialatif@nhs.net   
Sponsors and Collaborators
University College, London
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT03946722    
Other Study ID Numbers: 18/0458
First Posted: May 13, 2019    Key Record Dates
Last Update Posted: February 16, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Individual participant data will not be shared outside of the research group.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University College, London:
In vitro fertilisation
Assisted conception
Randomised controlled trial
Down-regulation
Additional relevant MeSH terms:
Layout table for MeSH terms
Adenomyosis
Uterine Diseases