Infertility, FemaleICSINCT03370068
The Role of ICSI in Non-male Factor Infertility in Advanced Maternal Age
A study testing ICSI and Conventional IVF in people with Infertility, Female, run by Dr. Tal Miller-Elkan at 1 site in Israel.
Trial summary
The use of Intracytoplasmic sperm injection (ICSI) has increased in the last decades regardless of the cause of infertility. Despite the increased use there is no clear evidence that ICIS is more effective than conventional in vitro fertilization (IVF) for non-male factor infertility. Read more about this study
- Who is it for?
- Ages 39 to 44 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Infertility, Female
- What is being tested?
- ICSI and Conventional IVF
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 69 participants
- Where
- 1 siteIsrael
- Study dates
- 1 Jan 2018to 1 Jul 2020
- 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 39 to 44 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Women between 39 to 44 years of age undergoing IVF treatments for non-male factor infertility.
Who cannot join
- Women undergoing IVF treatments for male factor infertility.
- Cases where PGD is planned.
- Women with a BMI above 40.
- Women younger then 39 years of age or older then 44 years of age.
- Women with a rate of fertilization bellow 50% in previous IVF cycles.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Role of Intracytoplasmic Sperm Injection in Non-male Factor Infertility in Maternal Age Above 39
The use of Intracytoplasmic sperm injection (ICSI) has increased in the last decades regardless of the cause of infertility. Despite the increased use there is no clear evidence that ICIS is more effective than conventional in vitro fertilization (IVF) for non-male factor infertility. The investigators therefore aim to perform a prospective randomized controlled study to compare between ICSI and conventional IVF in women between 39 to 44 years of age with non-male factor infertility.
Read the detailed description
ICSI is a method used in IVF in which a single sperm is injected directly into an oocyte. Originally ICSI was developed as a method for the treatment for couples with severe male factor infertility. In the last decades the use of ICSI has increased dramatically, especially for non-male factor infertility. In certain fertility clinics in the world ICSI is conducted in 100% of IVF cycles.
Despite the increased use of ICSI, there is no clear evidence that ICIS is more effective than conventional IVF for non-male factor infertility. There are currently few randomized controlled studies that compared the two modalities in the case of non-male factor infertility. In a randomized controlled trial that included 415 couples with non-male factor infertility and women younger than 37 years of age, conventional IVF was associated with better fertilization and implantation rates than ICSI but with comparable live birth rates. In addition, studies have not shown an advantage for ICSI over conventional IVF in the case of unexplained infertility, low oocyte yield or routine use to decrease the incidence of fertilization failure.
The proportion of women after the age of 35 undergoing IVF is constantly on the rise. Oocytes retrieved from older women are often of lower quality then oocytes retrieved from younger women. It is believed that due to the lower quality the fertilization rate is decreased in this population. However a recently published retrospective study including 745 women did not show an advantage for ICSI over conventional IVF. Contrary to what is believed, the conventional IVF group had a higher number of zygotes formed, more cycles with embryos transferred at the blastocyst stage and more cycles where embryos were available for cryopreservation.
The investigators therefore aim to perform a prospective randomized controlled study to compare between ICSI and conventional IVF in women between 39 to 44 years of age with non-male factor infertility. Male-factor infertility will be diagnosed according to the accepted semen analysis values included a semen concentration of 200 million/mL, progressive motility of 40% and a strict morphology of 4%. Patients will undergo standard clinical and hormonal investigation as usual for IVF. The treatment protocol will be in accordance with the decision of the attending physician, regardless of the research. Randomization will be between the ovaries of each patient. Following an informed consent a computer based randomization will allocate either ICSI or conventional IVF for each ovary so that for each study participant oocyte from one ovary will be randomly allocated to insemination by ICSI and the oocytes from the other ovary will be allocated to insemination by conventional IVF. As is customary in our IVF unit, 24, 72 and 96 hours after oocyte retrieval, the embryos will by studied by an embryologist for the number of cells and embryo quality.
- Conditions
- Infertility, Female
- Being tested
- ICSI, Conventional IVF
- Keywords
- ICSI, IVF, Infertility, non-male factor, intracytoplasmic sperm injection, In vitro fertilization
- Medical subject headings
- Infertility, Female, Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ICSIOther
Oocytes retrieved from one ovary will undergo insemination by ICSI.
Conventional IVFOther
Oocytes retrieved from the second ovary will undergo insemination by conventional IVF
| Study group | Role | What they receive |
|---|---|---|
| ICSI | Experimental | All the oocytes in this group (from one ovary) will undergo insemination by ICSI. Receives: Other: ICSI |
| Conventional IVF | Active comparator | All the oocytes in this group (from the other ovary) will undergo insemination by conventional IVF. Receives: Other: Conventional IVF |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fertilization rate
The rate of fertilized oocytes
Measured: 1 day
Secondary outcomes (5)
Embryos
Number of embryos day 2/3
Measured: 3-4 day
Top quality embryos
Number of top quality embryos day 2/3. Embryos will be defined as top quality if they will have four cells on Day 2 and/or 7 or 8 cells on Day 3, contain <20% fragmentation, and exhibited no apparent morphological abnormalities.
Measured: 3-4 days
Pregnancy
Pregnancy is defined as positive βhCG blood test 11-14 days after embryo transfer.
Measured: Approximately 2 weeks
Clinical pregnancy
Clinical pregnancy is defined as gestational sac seen on vaginal ultrasound scan by 6 weeks gestation.
Measured: Approximately 6 weeks
Pregnancy above 8 weeks gestation
Pregnancy above 8 weeks gestation with the appreance of a fetal pulse
Measured: Approximately 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2017
- Study start1 Jan 2018
- Primary completion1 Jul 2020
- Study completion1 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Infertility, FemaleStudies 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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr. Tal Miller-Elkan
- Sponsor type
- Other government
- Responsible party
- Sponsor-investigator, Dr. Tal Miller-Elkan, Sheba Medical Center
- Investigators
- Tal TE Elkan Miller, MD PhD, Principal investigator, Sheba Medical Cente
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03370068
- Sponsor's protocol ID
- SHEBA-17-4531-TEM-CTIL
- Acronym
- ICSI
- Status last verified
- Jul 2020
- First submitted
- 20 Nov 2017
- Last updated
- 28 Jul 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Palermo G, Joris H, Devroey P, Van Steirteghem AC. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet. 1992 Jul 4;340(8810):17-8. doi: 10.1016/0140-6736(92)92425-f.
PubMed 1351601Boulet SL, Mehta A, Kissin DM, Warner L, Kawwass JF, Jamieson DJ. Trends in use of and reproductive outcomes associated with intracytoplasmic sperm injection. JAMA. 2015 Jan 20;313(3):255-63. doi: 10.1001/jama.2014.17985.
PubMed 25602996Bhattacharya S, Hamilton MP, Shaaban M, Khalaf Y, Seddler M, Ghobara T, Braude P, Kennedy R, Rutherford A, Hartshorne G, Templeton A. Conventional in-vitro fertilisation versus intracytoplasmic sperm injection for the treatment of non-male-factor infertility: a randomised controlled trial. Lancet. 2001 Jun 30;357(9274):2075-9. doi: 10.1016/s0140-6736(00)05179-5.
PubMed 11445099Check JH, Yuan W, Garberi-Levito MC, Swenson K, McMonagle K. Effect of method of oocyte fertilization on fertilization, pregnancy and implantation rates in women with unexplained infertility. Clin Exp Obstet Gynecol. 2011;38(3):203-5.
PubMed 21995144Luna M, Bigelow C, Duke M, Ruman J, Sandler B, Grunfeld L, Copperman AB. Should ICSI be recommended routinely in patients with four or fewer oocytes retrieved? J Assist Reprod Genet. 2011 Sep;28(10):911-5. doi: 10.1007/s10815-011-9614-9. Epub 2011 Jul 27.
PubMed 21792665Fishel S, Aslam I, Lisi F, Rinaldi L, Timson J, Jacobson M, Gobetz L, Green S, Campbell A, Lisi R. Should ICSI be the treatment of choice for all cases of in-vitro conception? Hum Reprod. 2000 Jun;15(6):1278-83. doi: 10.1093/humrep/15.6.1278.
PubMed 10831555Korkmaz C, Tekin YB, Sakinci M, Ercan CM. Effects of maternal ageing on ICSI outcomes and embryo development in relation to oocytes morphological characteristics of birefringent structures. Zygote. 2015 Aug;23(4):550-5. doi: 10.1017/S0967199414000197. Epub 2014 May 29.
PubMed 24869767Tannus S, Son WY, Gilman A, Younes G, Shavit T, Dahan MH. The role of intracytoplasmic sperm injection in non-male factor infertility in advanced maternal age. Hum Reprod. 2017 Jan;32(1):119-124. doi: 10.1093/humrep/dew298. Epub 2016 Nov 16.
PubMed 27852688Haas J, Miller TE, Nahum R, Aizer A, Kirshenbaum M, Zilberberg E, Lebovitz O, Orvieto R. The role of ICSI vs. conventional IVF for patients with advanced maternal age-a randomized controlled trial. J Assist Reprod Genet. 2021 Jan;38(1):95-100. doi: 10.1007/s10815-020-01990-5. Epub 2020 Oct 28.
PubMed 33118102
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Intracytoplasmic Sperm Injection in Non-male Factor Infertility in Maternal Age Above 39
- ClinicalTrials.gov ID
- NCT03370068
- Acronym / sponsor ID
- ICSI / SHEBA-17-4531-TEM-CTIL
- Conditions
- Infertility, Female
- Keywords
- ICSI, IVF, Infertility, non-male factor, intracytoplasmic sperm injection, In vitro fertilization
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- Dr. Tal Miller-ElkanOther government
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- 1 Jul 2020 (actual)
- Study completion
- 1 Jul 2020 (actual)
- First posted
- 12 Dec 2017 (actual)
- 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.
The use of Intracytoplasmic sperm injection (ICSI) has increased in the last decades regardless of the cause of infertility. Despite the increased use there is no clear evidence that ICIS is more effective than conventional in vitro fertilization (IVF) for non-male factor infertility. The investigators therefore aim to perform a prospective randomized controlled study to compare between ICSI and conventional IVF in women between 39 to 44 years of age with non-male factor infertility.
Detailed description
ICSI is a method used in IVF in which a single sperm is injected directly into an oocyte. Originally ICSI was developed as a method for the treatment for couples with severe male factor infertility. In the last decades the use of ICSI has increased dramatically, especially for non-male factor infertility. In certain fertility clinics in the world ICSI is conducted in 100% of IVF cycles.
Despite the increased use of ICSI, there is no clear evidence that ICIS is more effective than conventional IVF for non-male factor infertility. There are currently few randomized controlled studies that compared the two modalities in the case of non-male factor infertility. In a randomized controlled trial that included 415 couples with non-male factor infertility and women younger than 37 years of age, conventional IVF was associated with better fertilization and implantation rates than ICSI but with comparable live birth rates. In addition, studies have not shown an advantage for ICSI over conventional IVF in the case of unexplained infertility, low oocyte yield or routine use to decrease the incidence of fertilization failure.
The proportion of women after the age of 35 undergoing IVF is constantly on the rise. Oocytes retrieved from older women are often of lower quality then oocytes retrieved from younger women. It is believed that due to the lower quality the fertilization rate is decreased in this population. However a recently published retrospective study including 745 women did not show an advantage for ICSI over conventional IVF. Contrary to what is believed, the conventional IVF group had a higher number of zygotes formed, more cycles with embryos transferred at the blastocyst stage and more cycles where embryos were available for cryopreservation.
The investigators therefore aim to perform a prospective randomized controlled study to compare between ICSI and conventional IVF in women between 39 to 44 years of age with non-male factor infertility. Male-factor infertility will be diagnosed according to the accepted semen analysis values included a semen concentration of 200 million/mL, progressive motility of 40% and a strict morphology of 4%. Patients will undergo standard clinical and hormonal investigation as usual for IVF. The treatment protocol will be in accordance with the decision of the attending physician, regardless of the research. Randomization will be between the ovaries of each patient. Following an informed consent a computer based randomization will allocate either ICSI or conventional IVF for each ovary so that for each study participant oocyte from one ovary will be randomly allocated to insemination by ICSI and the oocytes from the other ovary will be allocated to insemination by conventional IVF. As is customary in our IVF unit, 24, 72 and 96 hours after oocyte retrieval, the embryos will by studied by an embryologist for the number of cells and embryo quality.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ICSI | Experimental | Other: ICSIAll the oocytes in this group (from one ovary) will undergo insemination by ICSI. |
| Conventional IVF | Active comparator | Other: Conventional IVFAll the oocytes in this group (from the other ovary) will undergo insemination by conventional IVF. |
Who may qualify
- Ages
- 39 to 44 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Women between 39 to 44 years of age undergoing IVF treatments for non-male factor infertility.
Key exclusion criteria (5 listed)
- Women undergoing IVF treatments for male factor infertility.
- Cases where PGD is planned.
- Women with a BMI above 40.
- Women younger then 39 years of age or older then 44 years of age.
- Women with a rate of fertilization bellow 50% in previous IVF cycles.
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 |
|---|---|---|
| ICSIOocytes retrieved from one ovary will undergo insemination by ICSI. | Other | ICSI |
| Conventional IVFOocytes retrieved from the second ovary will undergo insemination by conventional IVF | Other | Conventional IVF |
Primary outcome
Fertilization rate
Time frame: 1 day
The rate of fertilized oocytes
5 secondary outcomes
Embryos
Time frame: 3-4 day
Top quality embryos
Time frame: 3-4 days
Pregnancy
Time frame: Approximately 2 weeks
Clinical pregnancy
Time frame: Approximately 6 weeks
Pregnancy above 8 weeks gestation
Time frame: Approximately 8 weeks
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 28 Jul 2020.
- Background: PubMed 1351601Palermo G, Joris H, Devroey P, Van Steirteghem AC. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet. 1992 Jul 4;340(8810):17-8. doi: 10.1016/0140-6736(92)92425-f.
- Background: PubMed 25602996Boulet SL, Mehta A, Kissin DM, Warner L, Kawwass JF, Jamieson DJ. Trends in use of and reproductive outcomes associated with intracytoplasmic sperm injection. JAMA. 2015 Jan 20;313(3):255-63. doi: 10.1001/jama.2014.17985.
- Background: PubMed 11445099Bhattacharya S, Hamilton MP, Shaaban M, Khalaf Y, Seddler M, Ghobara T, Braude P, Kennedy R, Rutherford A, Hartshorne G, Templeton A. Conventional in-vitro fertilisation versus intracytoplasmic sperm injection for the treatment of non-male-factor infertility: a randomised controlled trial. Lancet. 2001 Jun 30;357(9274):2075-9. doi: 10.1016/s0140-6736(00)05179-5.
- Background: PubMed 21995144Check JH, Yuan W, Garberi-Levito MC, Swenson K, McMonagle K. Effect of method of oocyte fertilization on fertilization, pregnancy and implantation rates in women with unexplained infertility. Clin Exp Obstet Gynecol. 2011;38(3):203-5.
- Background: PubMed 21792665Luna M, Bigelow C, Duke M, Ruman J, Sandler B, Grunfeld L, Copperman AB. Should ICSI be recommended routinely in patients with four or fewer oocytes retrieved? J Assist Reprod Genet. 2011 Sep;28(10):911-5. doi: 10.1007/s10815-011-9614-9. Epub 2011 Jul 27.
- Background: PubMed 10831555Fishel S, Aslam I, Lisi F, Rinaldi L, Timson J, Jacobson M, Gobetz L, Green S, Campbell A, Lisi R. Should ICSI be the treatment of choice for all cases of in-vitro conception? Hum Reprod. 2000 Jun;15(6):1278-83. doi: 10.1093/humrep/15.6.1278.
- Background: PubMed 24869767Korkmaz C, Tekin YB, Sakinci M, Ercan CM. Effects of maternal ageing on ICSI outcomes and embryo development in relation to oocytes morphological characteristics of birefringent structures. Zygote. 2015 Aug;23(4):550-5. doi: 10.1017/S0967199414000197. Epub 2014 May 29.
- Background: PubMed 27852688Tannus S, Son WY, Gilman A, Younes G, Shavit T, Dahan MH. The role of intracytoplasmic sperm injection in non-male factor infertility in advanced maternal age. Hum Reprod. 2017 Jan;32(1):119-124. doi: 10.1093/humrep/dew298. Epub 2016 Nov 16.
- Derived from this study: PubMed 33118102Haas J, Miller TE, Nahum R, Aizer A, Kirshenbaum M, Zilberberg E, Lebovitz O, Orvieto R. The role of ICSI vs. conventional IVF for patients with advanced maternal age-a randomized controlled trial. J Assist Reprod Genet. 2021 Jan;38(1):95-100. doi: 10.1007/s10815-020-01990-5. Epub 2020 Oct 28.
- 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.
Tal TE Elkan Miller, MD PhD principal investigator
Sheba Medical Cente
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ICSI and Conventional IVF in people with Infertility, Female, run by Dr. Tal Miller-Elkan at 1 site in Israel.
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 5 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 28 Jul 2020. 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 Israel. 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?
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?
Fertilization rate (time frame: 1 day). 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 NCT03370068, which also lists 9 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 28 Jul 2020.