Zishen Yutai Pill for Patients With Recurrent Implantation Failure

Official title

Zishen Yutai Pill for Patients With Recurrent Implantation Failure: a Randomized, Double-blind, Parallel-group, Placebo-controlled Trial

Overview

The goal of this clinical trial is to evaluate the efficacy of Zishen Yutai Pill (ZYP) on pregnancy outcomes following embryo transfer and its safety in patients with recurrent implantation failure. The main question it aims to answer is whether ZYP can improve live birth rate in participant's frozen embryo transfer (FET) cycles. Researchers will compare ZYP to a placebo (a look-alike substance with similar characteristics to ZYP) to see if it works to improve pregnancy outcomes. Participants will: 1. Start to receive ZYP or placebo (5g per time, 3 times daily) within the first 5 days of their initial menstrual cycle, and will undergo FET in the following cycle. The medication will be taken without interruption till the day of pregnancy test (2 weeks after embryo transfer). Patients with positive results in β-HCG test will continue to take the drug until clinical pregnancy confirmation by ultrasound three weeks later. For those with a negative β-HCG result, the intervention will be stopped. 2. Baseline visit will be conducted on days 2-4 of the participant's first menstrual cycle. Subsequent clinic visits will follow the standard protocol for FET cycle, as outlined below: Visit 1 (days 2-4 of the second menstrual cycle); Visit 2 (day of ovulation or day of endometrial transformation); Visit 3 (day of embryo transfer); Visit 4 (2 weeks after embryo transfer); Visit 5 (5 weeks after embryo transfer). Follow-up is scheduled at 10 weeks after embryo transfer (Visit 6) and after delivery (Visit 7), and these can be conducted remotely.

Interventions

• Drug Zishen Yutai Pill
  Eligible participants start to receive ZYP within the first 5 days of their initial menstrual cycle, and will undergo frozen-thawed embryo transfer (FET) in the following cycle. The medication will be taken without interruption till the day of pregnancy test (two weeks after embryo transfer). Patients with positive results in β-HCG test will continue to take the drug until clinical pregnancy confirmation by ultrasound three weeks later. For those with negative β-HCG results, the intervention wil
• Drug Placebo
  Eligible participants start to receive placebo within the first 5 days of their initial menstrual cycle, and will undergo frozen-thawed embryo transfer (FET) in the following cycle. The medication will be taken without interruption till the day of pregnancy test (two weeks after embryo transfer). Patients with positive results in β-HCG test will continue to take the drug until clinical pregnancy confirmation by ultrasound three weeks later. For those with negative β-HCG results, the intervention

Primary outcome measures

• Live birth rate [Time frame: About 40 weeks after embryo transfer, up to a maximum duration of 52 weeks after enrollment.]

Secondary outcome measures (12)

• Endometrial thickness (ovulation day/endometrial transformation day) [Time frame: On the day of ovulation (natural cycle) or on the day of endometrial transformation (HRT cycle), about 6 weeks after enrollment.]
• Endometrial pattern (ovulation day/endometrial transformation day) [Time frame: On the day of ovulation (natural cycle) or on the day of endometrial transformation (HRT cycle), about 6 weeks after enrollment.]
• Endometrial thickness (embryo transfer day) [Time frame: On the day of embryo transfer, about 6-7 weeks after enrollment.]
• Endometrial pattern (embryo transfer day) [Time frame: On the day of embryo transfer, about 6-7 weeks after enrollment.]
• β-HCG positive rate [Time frame: At 2 weeks after embryo transfer, about 8 weeks after enrollment.]
• Implantation rate [Time frame: At 5 weeks after embryo transfer, about 11 weeks after enrollment.]
• Clinical pregnancy rate [Time frame: At 5 weeks after embryo transfer, about 11 weeks after enrollment.]
• Ongoing pregnancy rate [Time frame: About 40 weeks after embryo transfer, up to a maximum duration of 52 weeks after enrollment.]
• Biochemical pregnancy loss rate [Time frame: At 5 weeks after embryo transfer, about 11 weeks after enrollment.]
• Clinical pregnancy loss rate [Time frame: About 40 weeks after embryo transfer, up to a maximum duration of 52 weeks after enrollment.]
• Gestational age at delivery [Time frame: About 40 weeks after embryo transfer, up to a maximum duration of 52 weeks after enrollment.]
• Birthweight [Time frame: About 40 weeks after embryo transfer, up to a maximum duration of 52 weeks after enrollment.]

Eligibility criteria

Inclusion criteria

• Meet the diagnostic criteria for recurrent implantation failure;
• Aged between 20-40 years old (inclusive) when oocytes were retrieved, and <43 at enrollment;
• Have at least 1 good-quality embryo for transfer;
• Intend to undergo frozen-thawed embryo transfer;
• Voluntary participation and signed informed consent.

Exclusion criteria

• Concomitant unresolved intrauterine lesions (e.g., intrauterine adhesions grade III-IV, endometrial polyps ≥1 cm, acute endometritis), endometriosis (ASRM stage ≥III), or adenomyosis (uterine volume ≥8 weeks of gestation) that affect embryo implantation;
• Intend to undergo FET after preimplantation genetic testing (PGT), including aneuploidy screening (PGT-A), monogenic disease testing (PGT-M), chromosomal structural rearrangement testing (PGT-SR);
• Thin endometrium (<7 mm) before enrollment;
• Concomitant severe genital malformations or genital neoplasms;
• Contraindications to estrogen and progestogen (e.g., history of breast cancer);
• Presence of medical contraindications to assisted reproductive technology, including that either partner has a severe psychiatric disorder, acute genitourinary tract infection, sexually transmitted disease, serious deleterious habit (e.g., drug abuse), or teratogenic exposure to radiation, toxic agent or medication that still under effect; or genetic diseases specified in the Law of the People's Republic of China on Maternal and Infant Health Care for which childbearing and PGT are contraindicated; or severe somatic diseases incompatible with pregnancy; or chromosomal abnormalities;
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 × the upper limit of normal (ULN), or serum creatinine (Scr) > ULN;
• Presence of poorly controlled severe systemic diseases, including cardiovascular, digestive, endocrine, and autoimmune diseases (e.g., antiphospholipid syndrome, Sjögren's syndrome, systemic lupus erythematosus, rheumatoid arthritis);
• Use of traditional Chinese medicines with similar functions and indications to ZYP within 1 month before screening that may affect treatment efficacy. Chinese patent medicines such as Tiaojing Cuyun Pills, Kuntai Capsules, Peikun Pills, Qilin Pills, Jinfeng Pills, Gushen Antai Pills, and Chinese herbal decoctions containing Cuscutae Semen, Dipsaci Radix, Taxilli Herba, and Asini Corii Colla with kidney-tonifying and spleen-strengthening effects;
• Allergy to any component of the study drugs;
• Participated in another interventional trials within 1 month prior to enrollment;
• Deemed unsuitable for this study by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 13 centers

• The First Affiliated Hospital of University of Science and Technology of China — Hefei
• Peking University Third Hospital — Beijing
• Peking University People's Hospital — Beijing
• Nanfang Hospital, Southern Medical University — Guangzhou
• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University — Guangzhou
• The Second Hospital of Hebei Medical University — Shijiazhuang
• The Second Affiliated Hospital of Zhengzhou University — Zhengzhou
• Xiangya Hospital of Central South University — Changsha
• … and 5 more centers

Identifiers

NCT: NCT07641088 · BYSZYYY.ZSYTW-HBT-2026

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗