How to reverse the dilemma of ovarian dysfunction in assisted reproduction?

Author: Lv Yan, First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital)

Qin Rujuan, The First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital)

Cai Xiaojing The First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital)

Reviewer: Zhang Huiqin, Chief Physician and Professor, First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital)

In the assisted reproductive clinic, we often encounter elderly patients with decreased ovarian reserve function. They have no embryos to transfer or do not become pregnant after transfer due to insensitivity to gonadotropin, few eggs obtained, and poor embryo quality. If you are such a patient, it is recommended that you can use the following comprehensive conditioning methods.

1. Adjust your lifestyle

Adjusting your lifestyle is the most basic method. Simply put, it means eating a balanced diet, keeping a normal schedule, exercising moderately, and taking appropriate supplements of vitamin E, dehydroepiandrosterone (DHEA), coenzyme Q10 and multiple vitamins to improve ovarian function and improve the quality of eggs.

2. Adjust your mindset

Patients who come to the reproductive center, especially female patients, are often under great pressure. However, we must also be clearly aware that anxiety, tension, and excessive stress are all causes of pregnancy failure. Maintaining a good attitude is particularly important for the adjustment of ovarian function. It is recommended that patients can cultivate hobbies and interests on weekdays to divert their attention from stress sources. If they find that they are under great pressure and often feel depressed, they can talk to relatives and friends to relieve stress, and seek help from professionals such as psychologists when necessary.

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3. Hyperbaric Oxygen Therapy

Hyperbaric oxygen therapy refers to a method of treating diseases by inhaling pure oxygen or high-concentration oxygen in a hyperbaric oxygen chamber.

In in vitro fertilization-embryo transfer (IVF-ET) treatment, hyperbaric oxygen can regulate endocrine disorders of the hypothalamus-pituitary-gonadal axis, improve endometrial receptivity, ovarian response, and egg quality, thereby achieving the goal of improving the success rate of assisted pregnancy.

Reasonable application of hyperbaric oxygen therapy can improve problems such as low ovarian reserve function, endometrial hypoplasia, and poor egg quality. Current studies have confirmed the effectiveness of hyperbaric oxygen therapy [1].

Adequate oxygen supply is necessary for normal oocyte maturation and chromosome arrangement in meiosis. Hyperbaric oxygen may enhance ischemia, promote oxidation-reduction reactions in hypoxic tissues, improve mitochondrial function, and reduce cell apoptosis.

For patients with poor ovarian function or who obtained few eggs or poor embryo quality during the last assisted reproductive process, doctors often recommend hyperbaric oxygen therapy 3 to 5 times a week and 15 to 20 times a month.

IV. Traditional Chinese Medicine

The role of traditional Chinese medicine such as Chinese herbal decoctions, Chinese patent medicines, acupuncture, and ointment prescriptions in improving ovarian function and increasing pregnancy rates has long been proven. According to traditional Chinese medicine theory, "kidneys govern reproduction," "liver is the innate nature of women," "spleen and stomach are the acquired foundations," "Ren governs the fetus," and "Chong is the sea of ​​blood and governs menstruation." Therefore, clinically, women's ovarian function can be regulated by tonifying the kidney and replenishing essence, soothing the liver and strengthening the spleen, and regulating Chong and Ren.

Among them, acupuncture can improve the endometrial receptivity by promoting the growth and development of the endometrium, reducing the blood flow resistance of the uterine artery, and thereby increasing the embryo implantation rate, clinical pregnancy rate, and live birth rate of assisted reproduction [2]. In addition, acupuncture can also relieve the anxiety, depression, and insomnia symptoms of infertile patients, thereby improving the quality of life of patients and facilitating pregnancy outcomes.

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5. Recombinant human growth hormone therapy

The "Guidelines for Clinical Practice of Assisted Reproduction for Elderly Infertile Women in China" points out that for patients with low ovarian reserve function and low ovarian response, recombinant human growth hormone can improve ovarian responsiveness and increase live birth rates, but the evidence is not sufficient at present. As a commonly used adjuvant therapy for patients undergoing in vitro fertilization-embryo transfer, recombinant human growth hormone can stimulate the growth of patients' follicles, enhance ovarian ovulation function, and improve oocyte quality.

Clinical studies [3] have shown that after pretreatment with recombinant human growth hormone, patients with diminished ovarian reserve function have increased ovarian responsiveness to exogenous gonadotropin, reduced the total amount and number of days of gonadotropin application, and increased endometrial thickness and receptivity.

It is recommended to apply recombinant human growth hormone in small doses (1-2U/day) from the 1st to 3rd day of the menstrual cycle one month in advance until the ovulation trigger day. This is a more common application scheme in recent years.

6. Artificial cycle therapy with estrogen and progesterone

Artificial cycle therapy is a treatment method that simulates an artificial menstrual cycle to regulate menstruation based on the normal secretion of estrogen and progesterone in the human body. Estrogen is usually used for 21 consecutive days, and progesterone preparations are given at the same time during the last 10 days of taking estrogen. This therapy can regulate the ovarian pituitary axis, inhibit the increase of endogenous follicle-stimulating hormone in the late luteal phase, improve the synchronization of follicle development in the early follicular phase, and promote the recruitment of follicles in the next test tube cycle.

Of course, doctors will also adjust the ovulation induction plan to improve the egg acquisition in the next test tube cycle. Through the above methods, some patients with low ovarian reserve function, low ovarian response, poor embryo quality in the previous cycle, etc. can get out of trouble, thereby improving the transplantation rate and pregnancy rate.

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References:

[1] Zhang Min, Wang Jian, Du Min, et al. Hyperbaric oxygen and in vitro fertilization-embryo transfer [J]. Medical Review, 2011, 17 (17): 2574-2575.

[2] Fan Su, Yang Huisheng, Fang Weigong, et al. Current status and thinking of acupuncture application in assisted reproduction in the United States [J]. Chinese Journal of Acupuncture, 2022, 42(2): 537-539.

[3] Lu Hongyan, Huang Yuhui, Cui Yanguo, et al. Effect of recombinant human growth hormone pretreatment on the outcome of in vitro fertilization-embryo transfer in patients with diminished ovarian reserve and poor ovarian response [J]. Chinese Journal of Maternal and Child Health, 2023, 38(6): 1060-1064.