Efficacy and Safety of Gushen Antai Pill on Ongoing Pregnancy Rate in Women With Normal Ovarian Reserve Undergoing IVF-ET

NCT ID: NCT04872660

Last Updated: 2024-09-04

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

PHASE4

Total Enrollment

800 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-06-15

Study Completion Date

2025-12-30

Brief Summary

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The purpose of this study is to investigate whether oral Gushen Antai pills supplementation for luteal phase support will improve ongoing pregnancy rate in women with normal ovarian reserve in fresh embryo transfer cycles.

Detailed Description

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Infertility is a growing reproductive health problem, and it is estimated that approximately 15% of couples of reproductive ages are affected. The invention and popularity of IVF-ET technology, although improving sperm egg encounter and fertilization barriers and implanting early embryos from the uterine cavity in vitro, still do not solve the problem of the uterine implantation environment or endometrial receptivity, and the pregnancy rate needs to be further improved. However, traditional Chinese medicine (TCM) has an original theoretical understanding and exact efficacy for gynecological diseases, therefore, it is necessary to supplement TCM interventions with endometrial receptivity as described above.

TCM is a kind of traditional treatment method with thousands of years history in China, and some previous studies have shown its unique experience in assisting pregnancy and reduce vaginal bleeding in early pregnancy . Similar to the notion of "hypothalamus- pituitary-ovary axis" that is established by Western medicine, TCM also has deeply studied the reproductive regulation of kidney and proposed the concept of "kidney-Tian Gui-Chong Ren-uterine axis." According to TCM, "Kidney Governs Reproduction," and female infertility is closely related to kidney deficiency, and the main therapeutic principle of it involves tonification of the kidney.

GSATP is widely used as an adjunctive therapy in women with threatened abortion in China and the clinical effects reflected by the patients remained satisfactory. The function of GSATP is nourishing yin and tonifying the kidney, strengthening Chong and prevent miscarriage. GSATP is used in the early threatened abortion, which belongs to the kidney yin deficiency syndrome of traditional Chinese medicine. GSATP is made up of Dodder, uncaria, Scutellaria, Atractylodes macrocephala, white peony, rehmannia, Polygonum multiflorum, Dipsacus, Cistanche deserticola, mulberry parasitism. The main components of GSATP include baicalin, Atractylodes macrocephala polysaccharide, flavonoids from Cuscuta chinensis, rhynchophylline, polysaccharides, Cistanche polysaccharides, stilbene glycosides and anthraquinone glycosides and triterpenoid saponins, etc. Modern pharmacological studies have found that these ingredients can improve vascular function, regulate immune activity, inhibit uterine contraction and improve ovarian endocrine function, so GSATP may play a role in promoting embryo implantation and preventing pregnancy. However, to improve the success rate of embryo implantation is a complex process and has not been fully studied. Therefore, in treating complex diseases, multi-targeted therapy such as TCM might have unique advantages over western medicine treatment alone. Although GSATP is associated with very good response in patients, lack of high-quality evidence-based medicine has restricted its promotion. The combination of evidence-based medicine, modern medicine and traditional Chinese medicine is a huge field that involves continuous attention and efforts.

GSATP dramatically increased the ongoing pregnancy rate and decreased the prevalence of vaginal bleeding in patients undergoing frozen thawed embryo transfer in our previous study. Recently, it was demonstrated that luteal support combined with GSATP could dramatically increase embryo implantation and clinical pregnancy rates, as well as early pregnancy loss rates, in IVF-ET fresh embryo transfer cycles. However, the study's methodological deficiencies prevented it from reaching a definitive conclusion about GSATP's treatment effect. This was mostly attributed to the unspecified randomization process, the absence of distribution concealment and blinding, no placebo control, and vague inclusion and exclusion criteria. As a result, a well-designed randomized clinical trial is essential to estimate the efficiency and safety of GSATP in optimizing reproductive outcomes in women with normal ovarian reserve during fresh embryo transfer cycles.

Conditions

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Infertility, Female

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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GSATP group

Gushen Antai Pill (GSATP, 6g\* 9 bags, Beijing boran Pharmaceutical Inc.) was required to be taken orally, 6g three times daily combined with vaginal progesterone (90 mg/day Crinone, Merck) from the day of embryo transfer until 10th gestational week.

Group Type EXPERIMENTAL

Gushen Antai Pill

Intervention Type DRUG

The Gushen Antai Pill (GSATP, Z20030144) is composed of 10 herbs including radix-polygoni multiflori, radix rehmanniae praeparata, cistanche salsa, radix dipsaci, uncaria, semen cuscutae, rhizoma atractylodis macrocephalae, radix scutellariae, radix paeoniae lactiflorae. Its production follows GMP standards and takes the form of water honey pills, each bag of 6g.

Placebo group

Placebo pill is made up of a certain amount of starch and glucose, and is shaped like GSATP according to the National Drug Standards of the State Food and Drug Administration of China. Placebo pill was required to be taken orally, 6g three times daily combined with vaginal progesterone (90 mg/day Crinone, Merck) from the day of embryo transfer until 10th gestational week.

Group Type PLACEBO_COMPARATOR

Placebo pill

Intervention Type DRUG

The placebo pill is produced by Beijing boran Pharmaceutical Co., Ltd. It can simulate the appearance, color and smell of GSATP formula, but it has no clinical effect because it has no active ingredients.

Interventions

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Gushen Antai Pill

The Gushen Antai Pill (GSATP, Z20030144) is composed of 10 herbs including radix-polygoni multiflori, radix rehmanniae praeparata, cistanche salsa, radix dipsaci, uncaria, semen cuscutae, rhizoma atractylodis macrocephalae, radix scutellariae, radix paeoniae lactiflorae. Its production follows GMP standards and takes the form of water honey pills, each bag of 6g.

Intervention Type DRUG

Placebo pill

The placebo pill is produced by Beijing boran Pharmaceutical Co., Ltd. It can simulate the appearance, color and smell of GSATP formula, but it has no clinical effect because it has no active ingredients.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patients with normal ovarian function reserve (5 ≤ AFC ≤ 15, 1.2 ng/ml ≤ AMH ≤ 3.5 ng/ml).
* Patients with regular menstrual cycle (21-35 days) and normal ovulation.
* Initial IVF / ICSI treatment.
* At least one embryo or blastocyst available for transfer.

Exclusion Criteria

* Age ≥ 43 years old.
* Body mass index (BMI) ≥ 28 Kg/m2.
* "Freeze-all" strategy.
* Those using the natural cycle or mild stimulation for IVF/ICSI treatment.
* Individuals with severe hyperstimulation ovarian syndrome during controlled ovarian stimulation.
* Acceptors of donated oocytes or performed either In vitro Maturation (IVM) or blastocyst biopsy for Preimplantation Genetic Diagnosis (PGD) or Preimplantation Genetic Testing for Aneuploidies (PGT-A).
* History of two or more previous consecutive spontaneous abortions.
* History of two or more previous IVF-ET failures.
* Karyotype abnormalities.
* Polycystic ovary syndrome.
* Presence of a non-surgically treated hydrosalpinx, uterine cavity fluid or endometrial polyp and an ovarian endometriosis cyst requiring surgery, during ovarian stimulation.
* Congenital or acquired abnormalities of uterine anatomy.
* Combined contraindications to assisted reproductive technology or pregnancy, such as uncontrolled abnormalities of liver and kidney function, diabetes mellitus (glycosylated haemoglobin ≤7%, fasting blood glucose \<10 mmol/L ), hypertension, thyroid disease, symptomatic heart disease, moderate to severe anaemia, history of malignancy or thromboembolism or propensity to thrombosis, severe psychiatric disorder, acute infections of the genitourinary system, sexually transmitted diseases, serious adverse habits such as drug abuse, exposure to teratogenic amounts of radiation, toxins, or drugs (such as prednisone or other hormones, adrenaline, antibiotics, or hypertension, cardiovascular, or antiviral medications) during the active procedure period , and uterine factor infertility or physical illness which prevents the ability to bear a pregnancy.
Minimum Eligible Age

21 Years

Maximum Eligible Age

42 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Shandong University of Traditional Chinese Medicine

OTHER

Sponsor Role lead

Responsible Party

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Jing-Yan Song

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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The Affiliated Hospital of Shandong University of Traditional Chinese Medicine

Jinan, Shandong, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Zhen-Gao Sun, M.D.

Role: CONTACT

+86-13708938621

Jing-Yan Song, M.D.

Role: CONTACT

+86-1876580013

Facility Contacts

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Zhen-Gao Sun, PhD

Role: primary

+8613708938621

References

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Inhorn MC, Patrizio P. Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century. Hum Reprod Update. 2015 Jul-Aug;21(4):411-26. doi: 10.1093/humupd/dmv016. Epub 2015 Mar 22.

Reference Type BACKGROUND
PMID: 25801630 (View on PubMed)

Ried K. Chinese herbal medicine for female infertility: an updated meta-analysis. Complement Ther Med. 2015 Feb;23(1):116-28. doi: 10.1016/j.ctim.2014.12.004. Epub 2015 Jan 3.

Reference Type BACKGROUND
PMID: 25637159 (View on PubMed)

Smith CA, Armour M, Ee C. Complementary Therapies and Medicines and Reproductive Medicine. Semin Reprod Med. 2016 Mar;34(2):67-73. doi: 10.1055/s-0035-1571194. Epub 2016 Feb 11.

Reference Type BACKGROUND
PMID: 26866600 (View on PubMed)

Shen L-H. Observation on the effect of Gushen Antai pill combined withprogesterone on Early Threatened Abortion [in Chinese]. Chin J Maternal Child HealthCare. 2012; 27:4628-9

Reference Type BACKGROUND

Qin D-N, She B-R, She Y-C. Effects of Flavonoids from Cuscuta chinensis on reproductivefunction of experimental animals and human villi [in Chinese]. Chin J New Drugs Clin Pharmacol. 2000; 11(6):349-51.

Reference Type BACKGROUND

Chen W-X, Chen S-H, Li W-J, Shu Q, Jiang D-Q. Modern pharmacological study on the sedative effect of baicalein andAtractylodes macrocephala [in Chinese]. J Clin Rational Drug Use. 2012; 5(12B):177-8.

Reference Type BACKGROUND

Ma B. Research progress on hypotensive effect and mechanism of Uncariarhynchophylla [in Chinese]. China Med Guide. 2011; 8(7):12-4.

Reference Type BACKGROUND

Wang P. Modern pharmacological research and clinical application of Rehmannia glutinosa [in Chinese]. Modern Distance Educ Trad Chin Med China. 2008; 6(8):986

Reference Type BACKGROUND

Cao XL, Song JY, Zhang XX, Chen YH, Teng YL, Liu HP, Deng TY, Sun ZG. Effects of a Chinese Patent Medicine Gushen'antai Pills on Ongoing Pregnancy Rate of Hormone Therapy FET Cycles: A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Front Endocrinol (Lausanne). 2020 Sep 23;11:581719. doi: 10.3389/fendo.2020.581719. eCollection 2020.

Reference Type BACKGROUND
PMID: 33071986 (View on PubMed)

Lu Y, Long XL. Clinical efficacy of Gushen Antai pill combined with progesterone after in vitro fertilization and embryo transfer [in Chinese]. Maternal and Child Health Care of China. 2017;32(9):1980-2.

Reference Type BACKGROUND

Xu Y, Hu X, Ai KL, Sun ZG, Song JY. Gushen Antai pill for expected normal ovarian responders undergoing IVF-ET (GSATP-FreET): interim analysis of a randomized controlled trial. Contracept Reprod Med. 2025 Mar 13;10(1):19. doi: 10.1186/s40834-025-00352-9.

Reference Type DERIVED
PMID: 40082945 (View on PubMed)

Other Identifiers

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SDUTCMSZG770214

Identifier Type: -

Identifier Source: org_study_id

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