InfertilityFORT-TNCT00246506
Infertility Therapy for Women Age Thirty-eight and Older
A study testing intrauterine insemination and in vitro fertilization in people with Infertility, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 38 to 43 yearsHealthy volunteers can take part
- Conditions the study is for
- Infertility
- What is being tested?
- intrauterine insemination and in vitro fertilization
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 450 participants
- Where
- 4 sitesUnited States
- Study dates
- Jul 2003to Apr 2013
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 38 to 43 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 10Show fewer
- 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.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Boston IVF
Brookline, Massachusetts, 02446
Boston IVF
Quincy, Massachusetts, 02169
Boston IVF
Waltham, Massachusetts, 02451
About this study
Official title: Optimal Infertility Therapy RCT: Women 40 and Older
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.
Read the 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
- Conditions
- Infertility
- Being tested
- intrauterine insemination, in vitro fertilization
- Keywords
- Infertility, Fertility, Reproduction, Advanced Maternal Age, Reproductive Medicine, Reproductive Techniques, Pregnancy
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
intrauterine inseminationProcedure or surgery
Also called IUI
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.
in vitro fertilizationProcedure or surgery
Also called assisted reproductive technologies
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.
| Study group | Role | What they receive |
|---|---|---|
| I. | Active comparator | 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. Receives: Procedure: intrauterine insemination; Procedure: in vitro fertilization |
| II. | Active comparator | 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. Receives: Procedure: intrauterine insemination; Procedure: in vitro fertilization |
| III. | Active comparator | Those couples randomized to (IVF) in vitro fertilization will bypass IUI treatments and start IVF therapy immediately. Receives: Procedure: in vitro fertilization |
What is being measured
The primary outcome is the main question the study is designed to answer.
Associated complications of treatment will be described.
Measured: at end of study
Secondary outcomes (1)
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.
Measured: at end of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2005 (estimated)
- Study startJul 2003
- Primary completionApr 2012
- Study completionApr 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for InfertilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 450 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Richard H. Reindollar, M.D., Principal investigator, Chair, Department of Obstetrics and Gynecology, Dartmouth-Hitchcock Medical Center, Dartmouth Medical School, Lebanon, New Hampshire
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00246506
- Sponsor's protocol ID
- 1R01HD044547
- Acronym
- FORT-T
- Status last verified
- Dec 2012
- First submitted
- 27 Oct 2005
- Last updated
- 15 Jan 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 16084887Nassar 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.
PubMed 34376578Goldman 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.
PubMed 24796764
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimal Infertility Therapy RCT: Women 40 and Older
- ClinicalTrials.gov ID
- NCT00246506
- Acronym / sponsor ID
- FORT-T / 1R01HD044547
- Conditions
- Infertility
- Keywords
- Infertility, Fertility, Reproduction, Advanced Maternal Age, Reproductive Medicine, Reproductive Techniques, Pregnancy
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 450 participants (estimated)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- Jul 2003
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2013 (estimated)
- First posted
- 31 Oct 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| I. | Active comparator | Procedure: intrauterine insemination, Procedure: in vitro fertilizationThose 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. |
| II. | Active comparator | Procedure: intrauterine insemination, Procedure: in vitro fertilizationThose 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. |
| III. | Active comparator | Procedure: in vitro fertilizationThose couples randomized to (IVF) in vitro fertilization will bypass IUI treatments and start IVF therapy immediately. |
Who may qualify
- Ages
- 38 to 43 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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).
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| intrauterine inseminationAlso: IUIAn 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. | Procedure or surgery | I., II. |
| in vitro fertilizationAlso: assisted reproductive technologiesThis 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. | Procedure or surgery | I., II., III. |
Primary outcome
Associated complications of treatment will be described.
Time frame: at end of study
1 secondary outcome
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2013.
- Background: PubMed 16084887Klipstein 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.
- Derived from this study: PubMed 34376578Nassar 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.
- Derived from this study: PubMed 24796764Goldman 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard H. Reindollar, M.D. principal investigator
Chair, Department of Obstetrics and Gynecology, Dartmouth-Hitchcock Medical Center, Dartmouth Medical School, Lebanon, New Hampshire
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing intrauterine insemination and in vitro fertilization in people with Infertility, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Associated complications of treatment will be described. (time frame: at end of study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00246506, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jan 2013.