SISTER: Sibling Oocyte Insemination With Frozen Sperm From Third Party Donors: Evaluation of Reproductive Techniques

NCT ID: NCT07175571

Last Updated: 2025-09-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

95 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-09-15

Study Completion Date

2026-05-01

Brief Summary

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The goal of this clinical trial is to learn whether two different methods of helping eggs and sperm join-intracytoplasmic sperm injection (ICSI) and conventional in vitro fertilization (IVF)-lead to better embryo development when using frozen donor sperm in people who do not have male fertility problems. The main questions it aims to answer are:

Does one method create more usable embryos (blastocysts) than the other?

Is there a difference in how often fertilization does not happen at all?

Do either of the methods lead to better embryo quality or early pregnancy?

Participants will:

Have their eggs divided into two groups. One group will be fertilized using ICSI (where a sperm is injected directly into an egg), and the other using conventional IVF (where eggs are mixed with sperm in a dish).

The fertilization method for each egg will be randomly assigned, with a random process also used to determine the assignment of any extra egg when an odd number is collected.

Continue regular fertility treatment while the study team compares the results of each fertilization method.

This study includes people with non-male factor infertility and uses frozen donor sperm. It hopes to learn whether ICSI, which is often used even when it may not be needed, truly helps improve outcomes compared to conventional IVF in these cases.

Detailed Description

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This is a prospective, randomized sibling-oocyte controlled trial designed to compare fertilization and embryo development outcomes between intracytoplasmic sperm injection (ICSI) and conventional in vitro fertilization (IVF) using cryopreserved donor sperm in non-male factor infertility cycles. Despite widespread use of ICSI in assisted reproductive technology (ART), there is insufficient evidence supporting its routine use in non-male factor indications, especially in cycles utilizing frozen sperm where male factor infertility is not a contributing variable.

The study aims to address ongoing clinical debate and practice variation by evaluating whether ICSI offers meaningful advantages over conventional IVF in this specific context. Previous retrospective and meta-analytic data have suggested that while ICSI may reduce total fertilization failure (TFF), it may not improve-and may even negatively impact-other key clinical outcomes such as blastulation rate, embryo quality, and early pregnancy rates in non-male factor populations. Additionally, concerns about increased pregnancy-related complications with ICSI have been raised.

To reduce inter-patient variability and enhance internal validity, a sibling-oocyte design will be employed, allowing within-patient comparison of insemination methods. Oocytes retrieved from each participant will be randomized to either ICSI or conventional IVF. Randomization will be conducted prior to oocyte retrieval using computer-generated allocation. For patients with an even number of mature oocytes, half will be assigned to each insemination method. For those with an odd number, the extra oocyte will be randomly allocated according to the pre-specified scheme.

The fertilization process will begin shortly after oocyte retrieval. In the conventional IVF arm, mature oocytes will be inseminated using washed frozen-thawed donor sperm at a standard concentration and co-incubated for 16-18 hours. In the ICSI arm, a single motile sperm will be injected directly into each mature oocyte. All oocytes will undergo standard embryological assessment post-insemination, and embryos will be cultured under identical conditions.

The primary endpoint is the blastulation rate, defined as the number of usable blastocysts (meeting lab criteria for cryopreservation or transfer) per number of oocytes inseminated in each arm. Secondary outcomes include:

* Fertilization rate: number of 2PN zygotes per oocyte inseminated
* Incidence of TFF: no oocytes fertilized in a given arm
* Proportion of high-quality blastocysts, defined as grade BB or higher
* Early clinical pregnancy rate, as determined by ultrasound-confirmed intrauterine gestation Statistical analysis will use generalized estimating equations (GEE) for the primary outcome at the oocyte level to account for clustering within patients. Secondary outcomes will be analyzed using chi-square or Fisher's exact tests as appropriate. All data will be analyzed on an intention-to-treat basis.

The study will enroll approximately 178 participants over 12 months at Shady Grove Fertility, where frozen donor sperm with normal post-thaw parameters is routinely available. Only non-male factor infertility patients using frozen donor sperm will be eligible, ensuring a controlled sperm quality baseline across study arms.

The hypothesis is that conventional IVF will demonstrate equivalent or superior blastulation rates compared to ICSI, with non-inferior fertilization outcomes and potentially better embryo morphology. Results from this trial will help refine clinical guidelines and may support a more evidence-based, resource-efficient use of ICSI.

IRB approval has been obtained, and informed consent will be secured from all participants. All procedures will adhere to Good Clinical Practice and applicable regulatory guidelines. Data confidentiality will be maintained throughout.

Conditions

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Infertility, Female Reproductive Techniques, Assisted Fertilization in Vitro

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

This is a randomized sibling-oocyte controlled trial in which each participant's retrieved oocytes are split between two insemination methods: intracytoplasmic sperm injection (ICSI) and conventional in vitro fertilization (IVF). Randomization occurs at the oocyte level, not at the participant level. For participants with an even number of mature oocytes, half are randomly assigned to ICSI and half to conventional IVF. For participants with an odd number, the extra oocyte is randomly allocated using a pre-specified scheme. This within-subject design allows direct comparison of fertilization and embryo development outcomes between the two methods while minimizing inter-patient variability.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Intracytoplasmic Sperm Injection (ICSI)

In this arm, a portion of each participant's mature oocytes will be inseminated using intracytoplasmic sperm injection (ICSI). A single frozen-thawed donor sperm cell will be injected directly into each oocyte using micromanipulation techniques. The oocyte assignment to ICSI will be determined through randomized sibling-oocyte allocation. Embryos will be cultured under standard laboratory conditions and assessed for fertilization (2PN), blastulation, embryo quality, and early clinical pregnancy outcomes.

Group Type EXPERIMENTAL

Intracytoplasmic Sperm Injection (ICSI)

Intervention Type PROCEDURE

Mature oocytes are injected with a single frozen-thawed donor sperm cell using micromanipulation under a microscope. This fertilization method is performed shortly after oocyte retrieval. Sperm used are pre-screened and standardized for post-thaw motility and morphology. ICSI is conducted in accordance with standard embryology lab protocols. The oocyte allocation to ICSI is randomized within each participant's cycle.

Conventional Insemination (IVF)

In this arm, a portion of each participant's oocytes will be inseminated using the conventional in vitro fertilization (IVF) method. Frozen-thawed donor sperm with normal post-thaw parameters will be co-incubated with oocytes in culture media for fertilization. The oocyte assignment to this method will be determined through randomized sibling-oocyte allocation. Embryos will be cultured under the same laboratory conditions and assessed for fertilization (2PN), blastulation, embryo quality, and early clinical pregnancy outcomes.

Group Type EXPERIMENTAL

Conventional Insemination (IVF)

Intervention Type PROCEDURE

Oocytes are inseminated by co-incubation with frozen-thawed donor sperm in a culture dish for 16-18 hours. Sperm are washed and prepared according to lab protocol to ensure motility and concentration suitability. This method does not involve direct sperm injection. Oocytes are randomly assigned to this method within each participant's retrieved cohort.

Interventions

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Intracytoplasmic Sperm Injection (ICSI)

Mature oocytes are injected with a single frozen-thawed donor sperm cell using micromanipulation under a microscope. This fertilization method is performed shortly after oocyte retrieval. Sperm used are pre-screened and standardized for post-thaw motility and morphology. ICSI is conducted in accordance with standard embryology lab protocols. The oocyte allocation to ICSI is randomized within each participant's cycle.

Intervention Type PROCEDURE

Conventional Insemination (IVF)

Oocytes are inseminated by co-incubation with frozen-thawed donor sperm in a culture dish for 16-18 hours. Sperm are washed and prepared according to lab protocol to ensure motility and concentration suitability. This method does not involve direct sperm injection. Oocytes are randomly assigned to this method within each participant's retrieved cohort.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Female patients undergoing IVF with frozen donor sperm at Shady Grove Fertility Center
* Normal ovarian reserve (AMH \> 1 ng/mL, AFC \> 10)
* Absence of male factor infertility
* Post-wash parameters: \>50% motility, \>5mil concentration
* \> 4 oocytes retrieved at time of transvaginal oocyte retrieval

Exclusion Criteria

* Donor Sperm with significant male factor infertility (e.g., abnormal sperm concentration, motility, or morphology)
* Any medical condition contraindicating ART
Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Shady Grove Fertility Reproductive Science Center

OTHER

Sponsor Role lead

Responsible Party

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Kate Devine

Medical Director and Chief Research Officer

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Kate Devine, MD

Role: STUDY_CHAIR

Shady Grove Fertility

Locations

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Shady Grove Fertility Rockville

Rockville, Maryland, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Allison Eubanks, MD

Role: CONTACT

301-400-2432

Tasha Newsome

Role: CONTACT

3015451289

Facility Contacts

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Tasha Newsome

Role: primary

301-545-1289

References

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Romero-Galisteo RP, Pinero-Pinto E, Palomo-Carrion R, Luque-Moreno C, Molina-Torres G, Gonzalez-Sanchez M. Translation, cross-cultural adaptation and validation of the Rett syndrome motor evaluation scale (RESMES): Spanish version. Eur J Paediatr Neurol. 2023 Nov;47:72-79. doi: 10.1016/j.ejpn.2023.09.008. Epub 2023 Sep 28.

Reference Type BACKGROUND
PMID: 37788534 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1351601 (View on PubMed)

Hao G, Zhou X, Yan H, Wang X, Qiao L, Ni D, Shu W, Yu T. Emotional experience elicited by direct electrical stimulation: Case series and literature review. Epilepsia Open. 2023 Jun;8(2):547-558. doi: 10.1002/epi4.12729. Epub 2023 Apr 4.

Reference Type BACKGROUND
PMID: 36932033 (View on PubMed)

Mao Z, Yao H, Zou Q, Zhang W, Dong Y. Digital Contact Tracing Based on a Graph Database Algorithm for Emergency Management During the COVID-19 Epidemic: Case Study. JMIR Mhealth Uhealth. 2021 Jan 22;9(1):e26836. doi: 10.2196/26836.

Reference Type BACKGROUND
PMID: 33460389 (View on PubMed)

Teodorescu M, Barnet JH, Hagen EW, Palta M, Young TB, Peppard PE. Association between asthma and risk of developing obstructive sleep apnea. JAMA. 2015 Jan 13;313(2):156-64. doi: 10.1001/jama.2014.17822.

Reference Type BACKGROUND
PMID: 25585327 (View on PubMed)

Mo DY, Tang YM, Wu EY, Tang V. Theoretical model of investigating determinants for a successful Electronic Assessment System (EAS) in higher education. Educ Inf Technol (Dordr). 2022;27(9):12543-12566. doi: 10.1007/s10639-022-11098-1. Epub 2022 Jun 3.

Reference Type BACKGROUND
PMID: 35676938 (View on PubMed)

Zhang R, Xu S, Yuan M, Guo L, Xie L, Liao Y, Xu Y, Fu X. An ultrasmall PVP-Fe-Cu-Ni-S nano-agent for synergistic cancer therapy through triggering ferroptosis and autophagy. Nanoscale. 2023 Aug 3;15(30):12598-12611. doi: 10.1039/d3nr02708b.

Reference Type BACKGROUND
PMID: 37462439 (View on PubMed)

Other Identifiers

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SISTER Study

Identifier Type: -

Identifier Source: org_study_id

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