InfertilityNCT03483298

Split Cohort Trial Comparing IVF Outcomes After the Use of Testicular vs. Ejaculated Sperm for ICSI

An observational study of Infertility, run by Reproductive Medicine Associates of New Jersey at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

The primary objective of this study is to determine if there is a difference in in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) outcomes when using testicular sperm versus ejaculated sperm in couples with elevated sperm DNA fragmentation after a failed in vitro fertilization (IVF) cycle Read more about this study

Who is it for?: Ages 18 to 65 years, men only
Conditions the study is for: Infertility
What is being tested?: ICSI
How many people: 7 participants
Where: 1 siteUnited States
Study dates: 23 Jun 2018to 31 Dec 2021
Phase: Observational
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 18 to 65 years
Men only
Adult, Older adult

Study population: Men with Elevated DNA fragmentation noted in ejaculated sperm (>25% DFI according to the American Society of Reproductive Medicine guidelines) and one prior failed IVF cycle

Who may be able to join

Willing to comply with all study procedures and be available for the duration of the study
Failed at least one IVF cycle (i.e., no live birth)
Elevated DNA fragmentation noted in ejaculated sperm (>25% DFI according to the American Society of Reproductive Medicine guidelines)
Couple electing single embryo transfer
Couples electing comprehensive chromosome screening (CCS) of embryos
At least 4 oocytes retrieved in IVF cycle in order to randomize

Who cannot join

Anything that would place the individual at increased risk or preclude the individual's full compliance with or completion of the study.
Contraindication to IVF
Clinical indication for preimplantation genetic diagnosis (PGD) (i.e., screening for single gene disorder, chromosomal translocation, or any other disorders requiring detailed embryo genetic analysis)
Male partner with azoospermia (<100,000 motile spermatozoa)
Male partner with Y-chromosome microdeletion
Male partner with any Karyotype other than 46,XY(normal male karyotype)

Show all 9Show fewer

Female partner history of hydrosalpinges or adnexal mass
Female partner history of endometrial insufficiency (max endometrial thickness < 7mm)
Female partner BMI < 35

Trial locations and contacts

1 site in 1 country.

United States1 site

IVI RMA New Jersey
Basking Ridge, New Jersey, 07920

Other trials in United States

About this study

Official title: Prospective Split Cohort Trial Comparing in Vitro Fertilization (IVF) Outcomes After the Use of Testicular Versus Ejaculated Sperm for ICSI in Med With Elevated DNA Fragmentation After a Failed IVF Cycle

Read the detailed description

The experimental design for this study is as follows:

Couples with male partners who will be undergoing a TESA procedure secondary to elevated DNA fragmentation (>25% DFI) as part of their routine IVF treatment will be contacted for possible study participation.
Informed consent will be obtained
The primary investigator will be notified of the couple's participation.
The male partner will cryopreserve an ejaculated semen sample if there is no cryopreserved ejaculated specimen in inventory. The male partner will undergo a surgical sperm retrieval (TESA) and the specimen will be frozen per routine.
Serum will be collected from the male partner and preserved for future analysis.
The cryopreserved pre-TESA ejaculate and TESA specimen will be thawed on the day of oocyte retrieval per protocol. After oocyte retrieval, oocytes will be analyzed per routine and assessed for maturity. The oocytes will be divided into two groups per embryologist discretion. One group will be labeled 'A' and the other will be labeled B.' A random letter generator will create a list of 'A' and 'B's which will be placed in sequentially numbered, sealed envelopes. The envelopes will be opened in sequence according to patient enrollment. The first envelope opened by the embryologist will reveal the letter of the oocyte group that will be inseminated with testicular sperm. The other group will be inseminated with the frozen/ thawed ejaculated sperm. Therefore, half of the oocytes will be inseminated using intracytoplasmic sperm injection (ICSI) with testicular sperm and the other half will be inseminated via ICSI with ejaculated sperm. If there are an odd number of oocytes, the extra oocyte will always belong to group A for simplicity.
If fertilized, the group of zygotes created using testicular sperm will take the group letter that corresponded to the testicular sperm. This will also be true of the zygotes using ejaculated sperm. Both groups of zygotes will be cultured to the blastocyst stage with culture conditions per standard laboratory procedures.
Fertilization and blastulation rates of the two groups will be recorded for each patient.
Each blastocyst will be biopsied for comprehensive chromosome screening (CCS) in routine fashion. Once comprehensive chromosomal screening results are available, if at least one euploid embryo is available, patients will undergo a single embryo transfer in a subsequent menstrual cycle.
Frozen embryo transfer cycles will be performed using either a programmed cycle (exogenous estradiol with subsequent progesterone) or a natural cycle to prepare the endometrium for embryo transfer.
If at least one euploid embryo is available from each group, a second randomization will occur at the time of embryo selection. The embryologist selecting the embryo for transfer will open a second sealed envelope, which contains the letter of the group from which the embryo for transfer should reside. The best quality embryo (per embryologist discretion) from the group corresponding to the letter in this envelope will be selected for transfer. The embryologist selecting the embryo will be blinded as to which group of embryos was created with ejaculated versus testicular sperm. The group from which the embryo selected for transfer was derived will be recorded.
Both the patient and the physician performing the embryo transfer will be blinded with regard to the group from which the embryo selected for transfer derived.
Pregnancy testing and follow up will proceed as per routine.
Approximately 8 weeks post-transfer, each participant will be assigned a cycle outcome (i.e., no pregnancy, miscarriage, ongoing pregnancy). At that time, the study participants can be notified of whether the sperm utilized for ICSI was derived from testicular sperm or ejaculated sperm. This information could be shared via telephone or in-person.

Conditions: Infertility
Being tested: ICSI
Medical subject headings: Infertility

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ICSIOther
The cryopreserved pre-TESA ejaculate and TESA specimen will be thawed on the day of oocyte retrieval per protocol for ICSI

Study groups in NCT03483298
Study group	Role	What they receive
elevated sperm DNA fragmentation		Couples with male partners who will be undergoing a TESA procedure secondary to elevated DNA fragmentation (>25% DFI) as part of their routine IVF treatment will have half of the women's eggs inseminated with ejaculated sperm and the other half with surgically obtained sperm via the ICSI procedure Receives: Other: ICSI

What is being measured

The primary outcome is the main question the study is designed to answer.

Blastulation Rate of testicular vs. ejaculated sperm after ICSI
# blast per 2 pronuclei in each group
Measured: 1 week post ICSI

Secondary outcomes (3)

Fertilization Rate
# fertilized per M2 in each group
Measured: 24 hrs post ICSI
Aneuploidy Rate
# abnormal embryos per useable blast in each group
Measured: approximately 2 weeks post trophectoderm biopsy
Clinical Pregnancy Rate
defined by presence of gestational sac and yolk sac in uterus on ultrasound
Measured: approximately 2 weeks post pregnancy test

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Jun 201831 Dec 2021

First posted30 Mar 2018
Study start23 Jun 2018
Primary completion31 Dec 2021
Study completion31 Dec 2021

Why it stopped: recruitment issues

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (6)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: Observational
Observational model: Cohort
Time perspective: Prospective
Enrolment: 7 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03483298
Sponsor's protocol ID: RMA-2018-04
Status last verified: Jan 2022
First submitted: 23 Mar 2018
Last updated: 28 Jan 2022
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Esteves SC, Sanchez-Martin F, Sanchez-Martin P, Schneider DT, Gosalvez J. Comparison of reproductive outcome in oligozoospermic men with high sperm DNA fragmentation undergoing intracytoplasmic sperm injection with ejaculated and testicular sperm. Fertil Steril. 2015 Dec;104(6):1398-405. doi: 10.1016/j.fertnstert.2015.08.028. Epub 2015 Oct 1.
PubMed 26428305
Greco E, Scarselli F, Iacobelli M, Rienzi L, Ubaldi F, Ferrero S, Franco G, Anniballo N, Mendoza C, Tesarik J. Efficient treatment of infertility due to sperm DNA damage by ICSI with testicular spermatozoa. Hum Reprod. 2005 Jan;20(1):226-30. doi: 10.1093/humrep/deh590. Epub 2004 Nov 11.
PubMed 15539441
Bradley CK, McArthur SJ, Gee AJ, Weiss KA, Schmidt U, Toogood L. Intervention improves assisted conception intracytoplasmic sperm injection outcomes for patients with high levels of sperm DNA fragmentation: a retrospective analysis. Andrology. 2016 Sep;4(5):903-10. doi: 10.1111/andr.12215. Epub 2016 May 27.
PubMed 27231097
Pabuccu EG, Caglar GS, Tangal S, Haliloglu AH, Pabuccu R. Testicular versus ejaculated spermatozoa in ICSI cycles of normozoospermic men with high sperm DNA fragmentation and previous ART failures. Andrologia. 2017 Mar;49(2). doi: 10.1111/and.12609. Epub 2016 Apr 25.
PubMed 27108915
Mehta A, Bolyakov A, Schlegel PN, Paduch DA. Higher pregnancy rates using testicular sperm in men with severe oligospermia. Fertil Steril. 2015 Dec;104(6):1382-7. doi: 10.1016/j.fertnstert.2015.08.008. Epub 2015 Sep 9.
PubMed 26363389
Lewis SE, John Aitken R, Conner SJ, Iuliis GD, Evenson DP, Henkel R, Giwercman A, Gharagozloo P. The impact of sperm DNA damage in assisted conception and beyond: recent advances in diagnosis and treatment. Reprod Biomed Online. 2013 Oct;27(4):325-37. doi: 10.1016/j.rbmo.2013.06.014. Epub 2013 Jul 11.
PubMed 23948450

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 28 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Prospective Split Cohort Trial Comparing in Vitro Fertilization (IVF) Outcomes After the Use of Testicular Versus Ejaculated Sperm for ICSI in Med With Elevated DNA Fragmentation After a Failed IVF Cycle
ClinicalTrials.gov ID: NCT03483298
Acronym / sponsor ID: RMA-2018-04
Conditions: Infertility
Study type: Observational
Recruitment status: TerminatedReason stopped: recruitment issues
Enrolment: 7 participants (actual)
Lead sponsor: Reproductive Medicine Associates of New JerseyUniversity, hospital or other
Study start: 23 Jun 2018 (actual)
Primary completion: 31 Dec 2021 (actual)
Study completion: 31 Dec 2021 (actual)
First posted: 30 Mar 2018 (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.

Detailed description

The experimental design for this study is as follows:

Couples with male partners who will be undergoing a TESA procedure secondary to elevated DNA fragmentation (>25% DFI) as part of their routine IVF treatment will be contacted for possible study participation.
Informed consent will be obtained
The primary investigator will be notified of the couple's participation.
The male partner will cryopreserve an ejaculated semen sample if there is no cryopreserved ejaculated specimen in inventory. The male partner will undergo a surgical sperm retrieval (TESA) and the specimen will be frozen per routine.
Serum will be collected from the male partner and preserved for future analysis.
The cryopreserved pre-TESA ejaculate and TESA specimen will be thawed on the day of oocyte retrieval per protocol. After oocyte retrieval, oocytes will be analyzed per routine and assessed for maturity. The oocytes will be divided into two groups per embryologist discretion. One group will be labeled 'A' and the other will be labeled B.' A random letter generator will create a list of 'A' and 'B's which will be placed in sequentially numbered, sealed envelopes. The envelopes will be opened in sequence according to patient enrollment. The first envelope opened by the embryologist will reveal the letter of the oocyte group that will be inseminated with testicular sperm. The other group will be inseminated with the frozen/ thawed ejaculated sperm. Therefore, half of the oocytes will be inseminated using intracytoplasmic sperm injection (ICSI) with testicular sperm and the other half will be inseminated via ICSI with ejaculated sperm. If there are an odd number of oocytes, the extra oocyte will always belong to group A for simplicity.
If fertilized, the group of zygotes created using testicular sperm will take the group letter that corresponded to the testicular sperm. This will also be true of the zygotes using ejaculated sperm. Both groups of zygotes will be cultured to the blastocyst stage with culture conditions per standard laboratory procedures.
Fertilization and blastulation rates of the two groups will be recorded for each patient.
Each blastocyst will be biopsied for comprehensive chromosome screening (CCS) in routine fashion. Once comprehensive chromosomal screening results are available, if at least one euploid embryo is available, patients will undergo a single embryo transfer in a subsequent menstrual cycle.
Frozen embryo transfer cycles will be performed using either a programmed cycle (exogenous estradiol with subsequent progesterone) or a natural cycle to prepare the endometrium for embryo transfer.
If at least one euploid embryo is available from each group, a second randomization will occur at the time of embryo selection. The embryologist selecting the embryo for transfer will open a second sealed envelope, which contains the letter of the group from which the embryo for transfer should reside. The best quality embryo (per embryologist discretion) from the group corresponding to the letter in this envelope will be selected for transfer. The embryologist selecting the embryo will be blinded as to which group of embryos was created with ejaculated versus testicular sperm. The group from which the embryo selected for transfer was derived will be recorded.
Both the patient and the physician performing the embryo transfer will be blinded with regard to the group from which the embryo selected for transfer derived.
Pregnancy testing and follow up will proceed as per routine.
Approximately 8 weeks post-transfer, each participant will be assigned a cycle outcome (i.e., no pregnancy, miscarriage, ongoing pregnancy). At that time, the study participants can be notified of whether the sperm utilized for ICSI was derived from testicular sperm or ejaculated sperm. This information could be shared via telephone or in-person.

Study design

Observational model: Cohort
Time perspective: Prospective
Number of arms: 1

Arm	Type	Receives
elevated sperm DNA fragmentation	–	Other: ICSICouples with male partners who will be undergoing a TESA procedure secondary to elevated DNA fragmentation (>25% DFI) as part of their routine IVF treatment will have half of the women's eggs inseminated with ejaculated sperm and the other half with surgically obtained sperm via the ICSI procedure

Who may qualify

Ages: 18 to 65 years
Sex: Male only
Age groups: Adult, Older adult
Study population: Men with Elevated DNA fragmentation noted in ejaculated sperm (>25% DFI according to the American Society of Reproductive Medicine guidelines) and one prior failed IVF cycle

Key inclusion criteria (6 listed)

Willing to comply with all study procedures and be available for the duration of the study
Failed at least one IVF cycle (i.e., no live birth)
Elevated DNA fragmentation noted in ejaculated sperm (>25% DFI according to the American Society of Reproductive Medicine guidelines)
Couple electing single embryo transfer
Couples electing comprehensive chromosome screening (CCS) of embryos

Key exclusion criteria (9 listed)

Anything that would place the individual at increased risk or preclude the individual's full compliance with or completion of the study.
Contraindication to IVF
Clinical indication for preimplantation genetic diagnosis (PGD) (i.e., screening for single gene disorder, chromosomal translocation, or any other disorders requiring detailed embryo genetic analysis)
Male partner with azoospermia (<100,000 motile spermatozoa)
Male partner with Y-chromosome microdeletion

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
ICSIThe cryopreserved pre-TESA ejaculate and TESA specimen will be thawed on the day of oocyte retrieval per protocol for ICSI	Other	elevated sperm DNA fragmentation

Primary outcome

Blastulation Rate of testicular vs. ejaculated sperm after ICSI
Time frame: 1 week post ICSI
# blast per 2 pronuclei in each group

3 secondary outcomes

Fertilization Rate
Time frame: 24 hrs post ICSI
Aneuploidy Rate
Time frame: approximately 2 weeks post trophectoderm biopsy
Clinical Pregnancy Rate
Time frame: approximately 2 weeks post pregnancy test

Results and safety

The study was stopped early (reason given: recruitment issues). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2022.
Background: PubMed 26428305Esteves SC, Sanchez-Martin F, Sanchez-Martin P, Schneider DT, Gosalvez J. Comparison of reproductive outcome in oligozoospermic men with high sperm DNA fragmentation undergoing intracytoplasmic sperm injection with ejaculated and testicular sperm. Fertil Steril. 2015 Dec;104(6):1398-405. doi: 10.1016/j.fertnstert.2015.08.028. Epub 2015 Oct 1.
Background: PubMed 15539441Greco E, Scarselli F, Iacobelli M, Rienzi L, Ubaldi F, Ferrero S, Franco G, Anniballo N, Mendoza C, Tesarik J. Efficient treatment of infertility due to sperm DNA damage by ICSI with testicular spermatozoa. Hum Reprod. 2005 Jan;20(1):226-30. doi: 10.1093/humrep/deh590. Epub 2004 Nov 11.
Background: PubMed 27231097Bradley CK, McArthur SJ, Gee AJ, Weiss KA, Schmidt U, Toogood L. Intervention improves assisted conception intracytoplasmic sperm injection outcomes for patients with high levels of sperm DNA fragmentation: a retrospective analysis. Andrology. 2016 Sep;4(5):903-10. doi: 10.1111/andr.12215. Epub 2016 May 27.
Background: PubMed 27108915Pabuccu EG, Caglar GS, Tangal S, Haliloglu AH, Pabuccu R. Testicular versus ejaculated spermatozoa in ICSI cycles of normozoospermic men with high sperm DNA fragmentation and previous ART failures. Andrologia. 2017 Mar;49(2). doi: 10.1111/and.12609. Epub 2016 Apr 25.
Background: PubMed 26363389Mehta A, Bolyakov A, Schlegel PN, Paduch DA. Higher pregnancy rates using testicular sperm in men with severe oligospermia. Fertil Steril. 2015 Dec;104(6):1382-7. doi: 10.1016/j.fertnstert.2015.08.008. Epub 2015 Sep 9.
Background: PubMed 23948450Lewis SE, John Aitken R, Conner SJ, Iuliis GD, Evenson DP, Henkel R, Giwercman A, Gharagozloo P. The impact of sperm DNA damage in assisted conception and beyond: recent advances in diagnosis and treatment. Reprod Biomed Online. 2013 Oct;27(4):325-37. doi: 10.1016/j.rbmo.2013.06.014. Epub 2013 Jul 11.
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.

Phil Cheng, MD principal investigator

IVI RMA

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Infertility, run by Reproductive Medicine Associates of New Jersey at 1 site 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 6 inclusion and 9 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: stopped early, as of the sponsor's last update on 28 Jan 2022. 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 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?

The study was stopped early (reason given: recruitment issues). 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?

Blastulation Rate of testicular vs. ejaculated sperm after ICSI (time frame: 1 week post ICSI). 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 NCT03483298, which also lists 6 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 Jan 2022; AzTrials last refreshed its copy on 29 Oct 2026.