Invitro FertilizationPhase 4NCT02674178
FSH/LH Ratio as a Predictor of IVF Outcome in Young and Older Women
A Phase 4 study testing Invitro fertilization in people with Invitro Fertilization, run by Cairo University at 1 site in Egypt.
Trial summary
All women had normal uterine cavity determined by previous hysterosalpingography or hysteroscopy. Women with abnormally low Gn as hypothalamic hypogonadism , High LH as PCOS and women with abnormal endocrine functions as abnormal thyroid or adrenal functions were excluded. Read more about this study
- Who is it for?
- Ages 20 to 40 years, women only
- Conditions the study is for
- Invitro Fertilization
- What is being tested?
- Invitro fertilization
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 235 participants
- Where
- 1 siteEgypt
- Study dates
- Jun 2012to May 2015
- Phase
- Phase 4
- 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 20 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- less than 41 years old , with normal menstrual cycle with a range of 24 - 35 days with day 3 FSH less than 10 mIU/ml in natural cycle and normal serum prolactin . All women had normal uterine cavity determined by previous hysterosalpingography or hysteroscopy
Who cannot join
- Women with abnormally low Gn as hypothalamic hypogonadism , High LH as PCOS and women with abnormal endocrine functions as abnormal thyroid or adrenal functions were excluded. Any woman with ovarian cyst or azopermic male partner was also excluded.
Trial locations and contacts
1 site in 1 country.
About this study
All women had normal uterine cavity determined by previous hysterosalpingography or hysteroscopy. Women with abnormally low Gn as hypothalamic hypogonadism , High LH as PCOS and women with abnormal endocrine functions as abnormal thyroid or adrenal functions were excluded. Any woman with ovarian cyst or azopermic male partner was also excluded.
The patients were subjected to history taking, including age, duration, type and cause of infertility and medical history. Full examination including general and abdominal and vaginal examination was done followed by ultrasound evaluation for presence of 3 or more pre-antral follicles and exclusion of ovarian cysts.
Read more
Basal day 3 hormonal evaluation for FSH, LH and E2 in a natural cycle was done. E2, FSH and LH levels were determined using Immulite system (Siemens Healthcare diagnostics,UK).The intra- and inter-assay coefficients of variation were 15% and 16% for E2, 4.8% and 26% for LH. FSH analytical sensitivity was 0.1 mIU/ml.
All participants underwent long protocol. Daily SC injection of Triptorelin : Decapeptyl 0.1 mg (Ferring, Switzerland) 0.1 mg started at day 21 of the cycle prior to stimulation cycle and continued till the day of hCG injection. Gn stimulation started after fulfilling stimulation start criteria of thin endometrium < 5 mm and low E2 < 50 and LH < 5IU/l [18] with either HMG(Menogon; Ferring, Switzerland) or rFSH (Gonal-f; Merck Serono, Germany) in a starting dose of 150-300 IU/day depending on patients age and previous gonadotropin response. then the dose was adjusted according to ovarian response monitored by serum E2 and ultrasound evaluation. All patients were followed up by Transvaginal ultrasound scan daily or on alternate days according to the ovarian response to treatment starting on treatment cycle day (6) for folliculometry and endometrial thickness and pattern.
Triggering by HCG 10000 IU IM (Pregnyl, Organon, the Netherlands) when at least 2 follicles reached a mean diameter of 18 mm [18]
Cycle cancellation was decided when transvaginal ultrasound scan on cycle day (9) revealed no adequate follicular growth (<3 mature follicles).
Ovum pick-up (OPU) was done 34-36 hours after hCG injection under transvaginal ultrasound guide.
Read the detailed description
All women had normal uterine cavity determined by previous hysterosalpingography or hysteroscopy. Women with abnormally low Gn as hypothalamic hypogonadism , High LH as PCOS and women with abnormal endocrine functions as abnormal thyroid or adrenal functions were excluded. Any woman with ovarian cyst or azopermic male partner was also excluded.
The patients were subjected to history taking, including age, duration, type and cause of infertility and medical history. Full examination including general and abdominal and vaginal examination was done followed by ultrasound evaluation for presence of 3 or more pre-antral follicles and exclusion of ovarian cysts.
Basal day 3 hormonal evaluation for FSH, LH and E2 in a natural cycle was done. E2, FSH and LH levels were determined using Immulite system (Siemens Healthcare diagnostics,UK).The intra- and inter-assay coefficients of variation were 15% and 16% for E2, 4.8% and 26% for LH. FSH analytical sensitivity was 0.1 mIU/ml.
All participants underwent long protocol. Daily SC injection of Triptorelin : Decapeptyl 0.1 mg (Ferring, Switzerland) 0.1 mg started at day 21 of the cycle prior to stimulation cycle and continued till the day of hCG injection. Gn stimulation started after fulfilling stimulation start criteria of thin endometrium < 5 mm and low E2 < 50 and LH < 5IU/l [18] with either HMG(Menogon; Ferring, Switzerland) or rFSH (Gonal-f; Merck Serono, Germany) in a starting dose of 150-300 IU/day depending on patients age and previous gonadotropin response. then the dose was adjusted according to ovarian response monitored by serum E2 and ultrasound evaluation. All patients were followed up by Transvaginal ultrasound scan daily or on alternate days according to the ovarian response to treatment starting on treatment cycle day (6) for folliculometry and endometrial thickness and pattern.
Triggering by HCG 10000 IU IM (Pregnyl, Organon, the Netherlands) when at least 2 follicles reached a mean diameter of 18 mm [18]
Cycle cancellation was decided when transvaginal ultrasound scan on cycle day (9) revealed no adequate follicular growth (<3 mature follicles).
Ovum pick-up (OPU) was done 34-36 hours after hCG injection under transvaginal ultrasound guide.
Metaphase II ocytes were analyzed. ICSI procedure was performed in all cases. Fertilization was assessed 16-18 h after ICSI and embryo quality was evaluated 2 and 3 days after ICSI was determined according to the number of blastomeres and the degree of fragmentation and multinucleation[19]. Oocytes were collected and embryos were cultured in ISM1culture medium (Origio medicult media, Denmark).
Transfer of cleaving embryos was done on day 3 after oocyte retrieval (using Labotect semi-rigid catheter; labotect GmbH, Germany) All patients received luteal support in the form of daily progesterone (Prontogest, Amsa, Italy) 100 mg IM daily starting from day of ovum retrieval [18] till day of hCG testing. Serum β hCG level was assessed on day 14 after ET .
The primary outcome parameters evaluated were clinical pregnancy (defined as the presence of gestational sac containing fetal hearts on ultrasound scan). Other parameters included occurrence of multiple pregnancy, Abortion and ectopic cases per pregnancies, dose of Gn, duration of stimulation, E2 and Progesterone levels at day of HCG triggering, endometrial thickness at day of HCG triggering, number of follicles > 16 mm , number of retrieved follicles , number of oocytes fertilized, number of good ET and cancellation rate.
The participants were divided according to age into 2 groups: Group 1<35 years old who are further subdivided according to FSH/LH ratio into G1A with FSH/LH ratio <2 and G1B with FSH/LH ratio ≥2. Group 2 ≥ 35 years old who are further subdivided according o FSH/LH ratio into G2A with FSH/LH ratio <2 and G2B with FSH/LH ratio ≥2. The use of cutoff value is supported by previous studies [20,21]
- Conditions
- Invitro Fertilization
- Being tested
- Invitro fertilization
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Invitro fertilizationProcedure or surgery
All participants underwent long protocol. Daily SC injection of Triptorelin 0.1 mg started at day 21 of the cycle prior to stimulation cycle and continued till the day of hCG injection. Gn stimulation started in a starting dose of 150-300 IU/day depending on patients age and previous gonadotropin response. then the dose was adjusted according to ovarian response monitored by serum E2 and ultrasound evaluation. All patients were followed up by Transvaginal ultrasound scan daily or on alternate days
Triggering by HCG 10000 IU IM when at least 2 follicles reached a mean diameter of 18 mm [18]
Ovum pick-up (OPU) was done 34-36 hours after hCG injection Transfer of cleaving embryos was done on day 3 after oocyte retrieval
| Study group | Role | What they receive |
|---|---|---|
| Age <35 | Active comparator | < 35 years old included 201 women who are further subdivided according o FSH/LH ratio into G1A (201 patients) with FSH/LH ratio <2 and G1B (37 patients) with FSH/LH ratio ≥2. Receives: Procedure: Invitro fertilization |
| Age ≥ 35 | Active comparator | . Group 2 ≥ 35 years old included 34 women who are further subdivided according o FSH/LH ratio into G2A (25 patients) with FSH/LH ratio <2 and G2B (9 patients) with FSH/LH ratio ≥2 Receives: Procedure: Invitro fertilization |
What is being measured
The primary outcome is the main question the study is designed to answer.
clinical pregnancy
the presence of gestational sac containing fetal hearts on ultrasound scan
Measured: 14 days after embryo transfer
Secondary outcomes (3)
multiple pregnancy
Measured: 14 days after embryo transfer
Abortion cases per pregnancies
Measured: 12 weeks after ET
ectopic cases per pregnancies
Measured: 4 weeks after ET
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2016 (estimated)
- Study startJun 2012
- Primary completionMay 2015
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Invitro FertilizationStudies of the same condition, open and under way.
- More trials run by Cairo UniversityThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 235 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cairo University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ahmed Maged, Cairo University
- Investigators
- Ahmed Maged, MD, Principal investigator, Kasr Alainy medical school
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02674178
- Sponsor's protocol ID
- 145
- Status last verified
- Feb 2016
- First submitted
- 31 Jan 2016
- Last updated
- 4 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- FSH/LH Ratio as a Predictor of IVF Outcome in Young and Older Women
- ClinicalTrials.gov ID
- NCT02674178
- Acronym / sponsor ID
- 145
- Conditions
- Invitro Fertilization
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 235 participants (actual)
- Lead sponsor
- Cairo UniversityUniversity, hospital or other
- Study start
- Jun 2012
- Primary completion
- May 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 4 Feb 2016 (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.
All women had normal uterine cavity determined by previous hysterosalpingography or hysteroscopy. Women with abnormally low Gn as hypothalamic hypogonadism , High LH as PCOS and women with abnormal endocrine functions as abnormal thyroid or adrenal functions were excluded. Any woman with ovarian cyst or azopermic male partner was also excluded.
The patients were subjected to history taking, including age, duration, type and cause of infertility and medical history. Full examination including general and abdominal and vaginal examination was done followed by ultrasound evaluation for presence of 3 or more pre-antral follicles and exclusion of ovarian cysts.
Basal day 3 hormonal evaluation for FSH, LH and E2 in a natural cycle was done. E2, FSH and LH levels were determined using Immulite system (Siemens Healthcare diagnostics,UK).The intra- and inter-assay coefficients of variation were 15% and 16% for E2, 4.8% and 26% for LH. FSH analytical sensitivity was 0.1 mIU/ml.
All participants underwent long protocol. Daily SC injection of Triptorelin : Decapeptyl 0.1 mg (Ferring, Switzerland) 0.1 mg started at day 21 of the cycle prior to stimulation cycle and continued till the day of hCG injection. Gn stimulation started after fulfilling stimulation start criteria of thin endometrium < 5 mm and low E2 < 50 and LH < 5IU/l [18] with either HMG(Menogon; Ferring, Switzerland) or rFSH (Gonal-f; Merck Serono, Germany) in a starting dose of 150-300 IU/day depending on patients age and previous gonadotropin response. then the dose was adjusted according to ovarian response monitored by serum E2 and ultrasound evaluation. All patients were followed up by Transvaginal ultrasound scan daily or on alternate days according to the ovarian response to treatment starting on treatment cycle day (6) for folliculometry and endometrial thickness and pattern.
Triggering by HCG 10000 IU IM (Pregnyl, Organon, the Netherlands) when at least 2 follicles reached a mean diameter of 18 mm [18]
Cycle cancellation was decided when transvaginal ultrasound scan on cycle day (9) revealed no adequate follicular growth (<3 mature follicles).
Ovum pick-up (OPU) was done 34-36 hours after hCG injection under transvaginal ultrasound guide.
Detailed description
All women had normal uterine cavity determined by previous hysterosalpingography or hysteroscopy. Women with abnormally low Gn as hypothalamic hypogonadism , High LH as PCOS and women with abnormal endocrine functions as abnormal thyroid or adrenal functions were excluded. Any woman with ovarian cyst or azopermic male partner was also excluded.
The patients were subjected to history taking, including age, duration, type and cause of infertility and medical history. Full examination including general and abdominal and vaginal examination was done followed by ultrasound evaluation for presence of 3 or more pre-antral follicles and exclusion of ovarian cysts.
Basal day 3 hormonal evaluation for FSH, LH and E2 in a natural cycle was done. E2, FSH and LH levels were determined using Immulite system (Siemens Healthcare diagnostics,UK).The intra- and inter-assay coefficients of variation were 15% and 16% for E2, 4.8% and 26% for LH. FSH analytical sensitivity was 0.1 mIU/ml.
All participants underwent long protocol. Daily SC injection of Triptorelin : Decapeptyl 0.1 mg (Ferring, Switzerland) 0.1 mg started at day 21 of the cycle prior to stimulation cycle and continued till the day of hCG injection. Gn stimulation started after fulfilling stimulation start criteria of thin endometrium < 5 mm and low E2 < 50 and LH < 5IU/l [18] with either HMG(Menogon; Ferring, Switzerland) or rFSH (Gonal-f; Merck Serono, Germany) in a starting dose of 150-300 IU/day depending on patients age and previous gonadotropin response. then the dose was adjusted according to ovarian response monitored by serum E2 and ultrasound evaluation. All patients were followed up by Transvaginal ultrasound scan daily or on alternate days according to the ovarian response to treatment starting on treatment cycle day (6) for folliculometry and endometrial thickness and pattern.
Triggering by HCG 10000 IU IM (Pregnyl, Organon, the Netherlands) when at least 2 follicles reached a mean diameter of 18 mm [18]
Cycle cancellation was decided when transvaginal ultrasound scan on cycle day (9) revealed no adequate follicular growth (<3 mature follicles).
Ovum pick-up (OPU) was done 34-36 hours after hCG injection under transvaginal ultrasound guide.
Metaphase II ocytes were analyzed. ICSI procedure was performed in all cases. Fertilization was assessed 16-18 h after ICSI and embryo quality was evaluated 2 and 3 days after ICSI was determined according to the number of blastomeres and the degree of fragmentation and multinucleation[19]. Oocytes were collected and embryos were cultured in ISM1culture medium (Origio medicult media, Denmark).
Transfer of cleaving embryos was done on day 3 after oocyte retrieval (using Labotect semi-rigid catheter; labotect GmbH, Germany) All patients received luteal support in the form of daily progesterone (Prontogest, Amsa, Italy) 100 mg IM daily starting from day of ovum retrieval [18] till day of hCG testing. Serum β hCG level was assessed on day 14 after ET .
The primary outcome parameters evaluated were clinical pregnancy (defined as the presence of gestational sac containing fetal hearts on ultrasound scan). Other parameters included occurrence of multiple pregnancy, Abortion and ectopic cases per pregnancies, dose of Gn, duration of stimulation, E2 and Progesterone levels at day of HCG triggering, endometrial thickness at day of HCG triggering, number of follicles > 16 mm , number of retrieved follicles , number of oocytes fertilized, number of good ET and cancellation rate.
The participants were divided according to age into 2 groups: Group 1<35 years old who are further subdivided according to FSH/LH ratio into G1A with FSH/LH ratio <2 and G1B with FSH/LH ratio ≥2. Group 2 ≥ 35 years old who are further subdivided according o FSH/LH ratio into G2A with FSH/LH ratio <2 and G2B with FSH/LH ratio ≥2. The use of cutoff value is supported by previous studies [20,21]
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Age <35 | Active comparator | Procedure: Invitro fertilization< 35 years old included 201 women who are further subdivided according o FSH/LH ratio into G1A (201 patients) with FSH/LH ratio <2 and G1B (37 patients) with FSH/LH ratio ≥2. |
| Age ≥ 35 | Active comparator | Procedure: Invitro fertilization. Group 2 ≥ 35 years old included 34 women who are further subdivided according o FSH/LH ratio into G2A (25 patients) with FSH/LH ratio <2 and G2B (9 patients) with FSH/LH ratio ≥2 |
Who may qualify
- Ages
- 20 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- less than 41 years old , with normal menstrual cycle with a range of 24 - 35 days with day 3 FSH less than 10 mIU/ml in natural cycle and normal serum prolactin . All women had normal uterine cavity determined by previous hysterosalpingography or hysteroscopy
Key exclusion criteria (1 listed)
- Women with abnormally low Gn as hypothalamic hypogonadism , High LH as PCOS and women with abnormal endocrine functions as abnormal thyroid or adrenal functions were excluded. Any woman with ovarian cyst or azopermic male partner was also 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 |
|---|---|---|
| Invitro fertilizationAll participants underwent long protocol. Daily SC injection of Triptorelin 0.1 mg started at day 21 of the cycle prior to stimulation cycle and continued till the day of hCG injection. Gn stimulation started in a starting dose of 150-300 IU/day depending on patients age and previous gonadotropin response. then the dose was adjusted according to ovarian response monitored by serum E2 and ultrasound evaluation. All patients were followed up by Transvaginal ultrasound scan daily or on alternate days Triggering by HCG 10000 IU IM when at least 2 follicles reached a mean diameter of 18 mm [18] Ovum pick-up (OPU) was done 34-36 hours after hCG injection Transfer of cleaving embryos was done on day 3 after oocyte retrieval | Procedure or surgery | Age <35, Age ≥ 35 |
Primary outcome
clinical pregnancy
Time frame: 14 days after embryo transfer
the presence of gestational sac containing fetal hearts on ultrasound scan
3 secondary outcomes
multiple pregnancy
Time frame: 14 days after embryo transfer
Abortion cases per pregnancies
Time frame: 12 weeks after ET
ectopic cases per pregnancies
Time frame: 4 weeks after ET
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2016.
- Individual participant dataSharing planned: No
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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.
Ahmed Maged, MD principal investigator
Kasr Alainy medical school
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Invitro fertilization in people with Invitro Fertilization, run by Cairo University at 1 site in Egypt.
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 1 inclusion and 1 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: finished, as of the sponsor's last update on 4 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
clinical pregnancy (time frame: 14 days after embryo transfer). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Feb 2016.