search
Back to results

Infertility Therapy for Women Age Thirty-eight and Older (FORT-T)

Primary Purpose

Infertility

Status
Unknown status
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
intrauterine insemination
in vitro fertilization
Sponsored by
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Infertility focused on measuring Infertility, Fertility, Reproduction, Advanced Maternal Age, Reproductive Medicine, Reproductive Techniques, Pregnancy

Eligibility Criteria

38 Years - 43 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion criteria: Female partner age from 38th to the 43rd birthday at the time of recruitment and six months of infertility. Male partner has a normal semen analysis showing at least 15 million total motile sperm/ejaculate and at least 1% normal forms by strict criteria, or at least 5 million total motile sperm in an IUI prep. Patients must have at least one ovary and at least one ipsilateral patent fallopian tube confirmed by HSG or laparoscopy. Pelvic pathology may be present but must be amenable to operative laparoscopy with the pelvis restored to a functional state, including surgically corrected stages I and II endometriosis. Patients with stage III endometriosis qualify only if the disease is limited to an isolated endometrioma in one or both ovaries and once removed the pelvis is restored to a functional state. For patients with a single patent fallopian tube, the open tube cannot have had a previous ectopic (tubal) pregnancy, and the closed tube cannot be a hydrosalpinx (a tube that is blocked at the end and filled with fluid), unless a cauterization has been performed at the junction of the uterus and fallopian tube. Alternatively, that tube could be removed. 4. Normal uterine cavity demonstrated by HSG, sonohysterogram (SHG), or hysteroscopy; pathology of the uterine cavity amenable to operative hysteroscopy (cavity restored to normal and demonstrated by postoperative study). Regular menstrual cycles ranging from 21 - 45 days (patients with occasional cycles, i.e. 1 -2 /year, outside this range will be acceptable). Acceptable ovarian reserve demonstrated in all patients by a clomiphene challenge test, i.e., cycle day 3 FSH/E2 values of <15 mIU/mL and <100 pg/mL, respectively, and cycle day 10 FSH < 15 mIU/ml. (Note: normal ovarian reserve is represented by FSH values less than 10-12 mIU/mL; our acceptable values represent the transition zone.) Normal TSH and prolactin levels. Informed consent from both partners. Female body mass index ≤ 38. Exclusion Criteria: Previous tubal or uterine cavity reconstructive surgery in which the pelvis or uterine cavity was not restored to functional. Unilateral or bilateral hydrosalpinx (a tube that is blocked at the end and filled with fluid) that has not had a cauterization performed at the junction of the uterus and fallopian tubes, or previous removal of a fallopian tube or an ovary. A laparoscopy that demonstrated pelvic adhesions or stage I or II endometriosis for which the pelvis could not be restored to normal by surgery, or endometriosis that was not ablated or excised. All patients with stage IV endometriosis, and those with stage III unless the disease is limited to an isolated endometrioma in one or both ovaries and once removed the pelvis is restored to a functional state. One or more prior ectopic pregnancies in which both affected tubes were rendered nonfunctional. One ectopic pregnancy if it existed in the single remaining tube. Two or more ectopic pregnancies even if both tubes are patent. Severe male factor (i.e. semen analysis not meeting criteria listed above). Couples using donor semen will be excluded Previous treatment with IUI or IVF or for normal ovulatory patients with gonadotropins. Inadequate ovarian reserve demonstrating FSH 15 mIU/mL or higher on cycle days 3 or 10 or estradiol 100 pg/mL or higher on cycle day 3. Anovulatory patients or those whose cycles are routinely < 21 days or > 45 days in length. Patients requiring gamete intrafallopian tube transfer (GIFT), zygote intrafallopian tube transfer (ZIFT), or tubal embryo transfer (TET). BMI greater than 38.

Sites / Locations

  • Brigham and Women's Hospital
  • Boston IVF
  • Boston IVF
  • Boston IVF

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

I.

II.

III.

Arm Description

Those randomized to have clomiphene/IUI treatments first will initiate therapy with two cycles of the fertility pill called clomiphene combined with (IUI) intrauterine insemination. If not pregnant after 2 IUI cycles, the couples will then proceed to IVF.

Those randomized to have gonadotropins/IUI treatments first will initiate therapy with two cycles of the fertility injections called FSH or gonadotropins combined with (IUI) intrauterine insemination. If not pregnant after 2 IUI cycles, the couples will then proceed to IVF.

Those couples randomized to (IVF) in vitro fertilization will bypass IUI treatments and start IVF therapy immediately.

Outcomes

Primary Outcome Measures

Associated complications of treatment will be described.

Secondary Outcome Measures

Demographics and baseline variables will be collected, including: medical and reproductive, history, age, education, income, race, nutritional history, smoking history, and clinical variables related to infertility diagnosis and treatment.

Full Information

First Posted
October 27, 2005
Last Updated
January 14, 2013
Sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
search

1. Study Identification

Unique Protocol Identification Number
NCT00246506
Brief Title
Infertility Therapy for Women Age Thirty-eight and Older
Acronym
FORT-T
Official Title
Optimal Infertility Therapy RCT: Women 40 and Older
Study Type
Interventional

2. Study Status

Record Verification Date
December 2012
Overall Recruitment Status
Unknown status
Study Start Date
July 2003 (undefined)
Primary Completion Date
April 2012 (Actual)
Study Completion Date
April 2013 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study will determine the most effective treatment strategy for infertile couples who present when the female partner is 38 years to the 43rd birthday and the couples are determined to have a reasonable chance for success.
Detailed Description
We hypothesize that infertile couples with the female partner 38-43 years of age and demonstrating an adequate ovarian reserve will have higher pregnancy rates at no more cost through immediate IVF than they would through infertility treatment in which IVF is preceded by either two cycles of clomiphene with IUI or two cycles of FSH with IUI. This hypothesis is being tested by conducting a randomized clinical trial of couples in which the female partner between her 38th and 43rd birthday and determined to have normal ovarian reserve by CCT, and who would otherwise be candidates for ovulation induction/IUI as their initial treatment. The trial will evaluate the efficacy, cost and cost-effectiveness of three alternative infertility treatment strategies: (1) two cycles of clomiphene/IUI followed by IVF, (2) two cycles of FSH/IUI followed by IVF, and (3) immediate IVF; the IVF treatment will include a maximum of four fresh cycles of IVF and two thaw cycles. The trial has the following specific aims: Aim 1: To compare the proportion of women with a clinically recognized intrauterine pregnancy after two cycles of treatment with clomiphene/IUI, FSH/IUI, or IVF. Aim 2: To evaluate the overall effectiveness of the three treatment strategies, and their associated complications. Aim 3: To evaluate the costs and cost effectiveness of the three treatment strategies, including direct and indirect medical costs. The study participants will be involved in the study for varying amounts of time. The duration of the study will be determined by the treatment cycle in which the participant becomes pregnant. It could be as short as several months' treatment plus the duration of the pregnancy or it could be as long as several years if the participant does not get pregnant or takes breaks during treatment. This is a collaborative study between Dartmouth College, Boston IVF, Brigham and Women's Hospital, Blue Cross Blue Shield of Massachusetts, Harvard Pilgrim Health Care, and Tufts Health Plan. Total expected enrollment: 450 Couples

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infertility
Keywords
Infertility, Fertility, Reproduction, Advanced Maternal Age, Reproductive Medicine, Reproductive Techniques, Pregnancy

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
450 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
I.
Arm Type
Active Comparator
Arm Description
Those randomized to have clomiphene/IUI treatments first will initiate therapy with two cycles of the fertility pill called clomiphene combined with (IUI) intrauterine insemination. If not pregnant after 2 IUI cycles, the couples will then proceed to IVF.
Arm Title
II.
Arm Type
Active Comparator
Arm Description
Those randomized to have gonadotropins/IUI treatments first will initiate therapy with two cycles of the fertility injections called FSH or gonadotropins combined with (IUI) intrauterine insemination. If not pregnant after 2 IUI cycles, the couples will then proceed to IVF.
Arm Title
III.
Arm Type
Active Comparator
Arm Description
Those couples randomized to (IVF) in vitro fertilization will bypass IUI treatments and start IVF therapy immediately.
Intervention Type
Procedure
Intervention Name(s)
intrauterine insemination
Other Intervention Name(s)
IUI
Intervention Description
An assisted reproduction technique which deposits washed sperm directly into the uterus, bypassing the cervix, and allowing the sperm to enter the fallopian tubes where fertilization normally occurs.
Intervention Type
Procedure
Intervention Name(s)
in vitro fertilization
Other Intervention Name(s)
assisted reproductive technologies
Intervention Description
This procedure involves stimulating the ovaries, retrieving released eggs, fertilizing the eggs, growing the embryos in a laboratory, and then implanting the embryos in the woman's uterus to develop naturally.
Primary Outcome Measure Information:
Title
Associated complications of treatment will be described.
Time Frame
at end of study
Secondary Outcome Measure Information:
Title
Demographics and baseline variables will be collected, including: medical and reproductive, history, age, education, income, race, nutritional history, smoking history, and clinical variables related to infertility diagnosis and treatment.
Time Frame
at end of study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
38 Years
Maximum Age & Unit of Time
43 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion criteria: Female partner age from 38th to the 43rd birthday at the time of recruitment and six months of infertility. Male partner has a normal semen analysis showing at least 15 million total motile sperm/ejaculate and at least 1% normal forms by strict criteria, or at least 5 million total motile sperm in an IUI prep. Patients must have at least one ovary and at least one ipsilateral patent fallopian tube confirmed by HSG or laparoscopy. Pelvic pathology may be present but must be amenable to operative laparoscopy with the pelvis restored to a functional state, including surgically corrected stages I and II endometriosis. Patients with stage III endometriosis qualify only if the disease is limited to an isolated endometrioma in one or both ovaries and once removed the pelvis is restored to a functional state. For patients with a single patent fallopian tube, the open tube cannot have had a previous ectopic (tubal) pregnancy, and the closed tube cannot be a hydrosalpinx (a tube that is blocked at the end and filled with fluid), unless a cauterization has been performed at the junction of the uterus and fallopian tube. Alternatively, that tube could be removed. 4. Normal uterine cavity demonstrated by HSG, sonohysterogram (SHG), or hysteroscopy; pathology of the uterine cavity amenable to operative hysteroscopy (cavity restored to normal and demonstrated by postoperative study). Regular menstrual cycles ranging from 21 - 45 days (patients with occasional cycles, i.e. 1 -2 /year, outside this range will be acceptable). Acceptable ovarian reserve demonstrated in all patients by a clomiphene challenge test, i.e., cycle day 3 FSH/E2 values of <15 mIU/mL and <100 pg/mL, respectively, and cycle day 10 FSH < 15 mIU/ml. (Note: normal ovarian reserve is represented by FSH values less than 10-12 mIU/mL; our acceptable values represent the transition zone.) Normal TSH and prolactin levels. Informed consent from both partners. Female body mass index ≤ 38. Exclusion Criteria: Previous tubal or uterine cavity reconstructive surgery in which the pelvis or uterine cavity was not restored to functional. Unilateral or bilateral hydrosalpinx (a tube that is blocked at the end and filled with fluid) that has not had a cauterization performed at the junction of the uterus and fallopian tubes, or previous removal of a fallopian tube or an ovary. A laparoscopy that demonstrated pelvic adhesions or stage I or II endometriosis for which the pelvis could not be restored to normal by surgery, or endometriosis that was not ablated or excised. All patients with stage IV endometriosis, and those with stage III unless the disease is limited to an isolated endometrioma in one or both ovaries and once removed the pelvis is restored to a functional state. One or more prior ectopic pregnancies in which both affected tubes were rendered nonfunctional. One ectopic pregnancy if it existed in the single remaining tube. Two or more ectopic pregnancies even if both tubes are patent. Severe male factor (i.e. semen analysis not meeting criteria listed above). Couples using donor semen will be excluded Previous treatment with IUI or IVF or for normal ovulatory patients with gonadotropins. Inadequate ovarian reserve demonstrating FSH 15 mIU/mL or higher on cycle days 3 or 10 or estradiol 100 pg/mL or higher on cycle day 3. Anovulatory patients or those whose cycles are routinely < 21 days or > 45 days in length. Patients requiring gamete intrafallopian tube transfer (GIFT), zygote intrafallopian tube transfer (ZIFT), or tubal embryo transfer (TET). BMI greater than 38.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard H. Reindollar, M.D.
Organizational Affiliation
Chair, Department of Obstetrics and Gynecology, Dartmouth-Hitchcock Medical Center, Dartmouth Medical School, Lebanon, New Hampshire
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Boston IVF
City
Brookline
State/Province
Massachusetts
ZIP/Postal Code
02446
Country
United States
Facility Name
Boston IVF
City
Quincy
State/Province
Massachusetts
ZIP/Postal Code
02169
Country
United States
Facility Name
Boston IVF
City
Waltham
State/Province
Massachusetts
ZIP/Postal Code
02451
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
16084887
Citation
Klipstein S, Regan M, Ryley DA, Goldman MB, Alper MM, Reindollar RH. One last chance for pregnancy: a review of 2,705 in vitro fertilization cycles initiated in women age 40 years and above. Fertil Steril. 2005 Aug;84(2):435-45. doi: 10.1016/j.fertnstert.2005.02.020.
Results Reference
background
PubMed Identifier
34376578
Citation
Nassar KW, Hintzsche JD, Bagby SM, Espinoza V, Langouet-Astrie C, Amato CM, Chimed TS, Fujita M, Robinson W, Tan AC, Schweppe RE. Targeting CDK4/6 Represents a Therapeutic Vulnerability in Acquired BRAF/MEK Inhibitor-Resistant Melanoma. Mol Cancer Ther. 2021 Oct;20(10):2049-2060. doi: 10.1158/1535-7163.MCT-20-1126. Epub 2021 Aug 10.
Results Reference
derived
PubMed Identifier
24796764
Citation
Goldman MB, Thornton KL, Ryley D, Alper MM, Fung JL, Hornstein MD, Reindollar RH. A randomized clinical trial to determine optimal infertility treatment in older couples: the Forty and Over Treatment Trial (FORT-T). Fertil Steril. 2014 Jun;101(6):1574-81.e1-2. doi: 10.1016/j.fertnstert.2014.03.012. Epub 2014 Apr 30.
Results Reference
derived

Learn more about this trial

Infertility Therapy for Women Age Thirty-eight and Older

We'll reach out to this number within 24 hrs