According to WHO standards, a man and a woman of childbearing age who live together after marriage and have normal sexual intercourse without using contraception and have not conceived for more than one year is called infertility. The latest survey shows that the incidence of infertility is 10%-15% of newlyweds. Most of the newly married couples with infertility who have not been treated with medication or surgery are seeking assisted reproductive technology to help them conceive. Assisted reproductive technology refers to a series of techniques to treat infertility through manipulation of eggs, sperm, fertilized eggs and embryos. It can be divided into two categories: artificial insemination, in vitro fertilization-embryo transfer (IVF-ET, commonly known as in vitro fertilization) and derivative techniques. Prior to the implementation of these two assisted reproductive techniques, ovulation promotion is usually performed with medication. Many infertile couples are unfamiliar with and afraid of ovulation promotion, so what is it all about? Why is ovulation promotion necessary? To understand the purpose and meaning of ovulation promotion, we should first understand the natural state of the menstrual cycle and ovulation. Throughout the menstrual cycle, there is only one ovulation opportunity in the middle of the menstrual cycle, usually one mature egg from the left or right ovary, and in rare cases, one mature egg from each ovary (if both eggs are successfully fertilized, it is usually called dizygotic twins). Since only one egg is expelled per menstrual cycle, the natural success rate of pregnancy per menstrual cycle is very low, averaging only 10-20%.
Obviously, if the natural menstrual cycle is used during assisted reproductive technology treatment, there is usually only one egg available, which severely limits the chances of final embryo transfer and the number of embryos that can be transferred, which often results in a low success rate and a significant increase in cost. Superovulation, also known as controlled ovarian stimulation, is a pharmacological method to break the natural cycle limits and induce multiple follicles to develop and mature simultaneously in a single menstrual cycle within a controlled range, increasing the number of eggs available for in vitro fertilization and the number of embryos available for transfer, and increasing pregnancy rates. The introduction of superovulation into assisted reproductive technology has played an important role in improving the success rate of in vitro fertilization and embryo transfer techniques and in the establishment and development of modern assisted reproductive technology, thus laying the foundation for a series of assisted reproductive technologies and becoming one of the routine and basic techniques in assisted reproductive technology. Which groups of people are suitable for ovulation promotion? It can be said that except for a small number of patients with contraindications, the vast majority of infertile couples are suitable for ovulation treatment. Contraindications include the following: first, patients with low ovarian function, premature ovarian failure, or ovarian gonadotropin resistance syndrome, who do not respond well to ovulatory drugs and cannot achieve the goal of multiple follicle development even with high doses of ovulatory drugs. Second, patients with ovarian tumors and other estrogen-dependent malignancies (e.g. breast cancer, endometrial cancer, cervical cancer, etc.), as ovulatory drugs act directly or indirectly on the hypothalamic-pituitary-gonadal axis, these drugs have adverse effects on these tumors. Thirdly, in patients with acute pelvic inflammatory disease or serious systemic diseases, the purpose of ovulation medication is pregnancy, and these patients are not suitable for pregnancy, so there is no significance of ovulation promotion. What are the methods to promote ovulation? In the past, a very small number of patients with polycystic ovary syndrome could be helped to ovulate by ovarian perforation and ovarian wedge resection, but at present, almost all patients use different kinds of drugs to promote ovulation according to different indications. However, the aim of all these drugs is to induce the development and maturation of multiple follicles in a menstrual cycle within a controlled range by enhancing endogenous gonadotropins, or suppressing endogenous gonadotropins altogether with a large amount of exogenous gonadotropins. In addition, there are some adjuvant pro-ovulatory drugs that are used mainly to increase the sensitivity of pro-ovulatory drugs or to regulate the endometrial tolerance, or for post-assisted reproductive technology fertility preservation treatment. What are the side effects of ovulation medication abuse? As mentioned earlier, ovulation medications artificially interfere with the hypothalamic-pituitary-gonadal axis, and this external intervention may have some side effects or pose a risk of long-term disease. The most common side effect of ovulatory medication is ovarian hyperstimulation syndrome. The goal of ovulation stimulation itself is to achieve an ovarian response that is beyond physiological levels, but within a controlled or regulated range, resulting in more eggs and more embryos available for transfer with a higher success rate. However, this response is beyond regulation, i.e., the “over” response can be caused by severe systemic changes or excessive estrogen levels and high estrogen/luteinizing hormone ratios during the luteal phase, which can lead to severe systemic conditions and impair embryo implantation. Ovarian hyperstimulation syndrome is one of the major complications of assisted reproduction with in vitro fertilization. It is usually seen during gonadotropin (HMG/HMG+hCG, etc.) treatment and can be life-threatening in severe cases, including nausea, vomiting, abdominal discomfort, weight gain, ovarian enlargement, thoracoabdominal effusion, oliguria, disturbed water-electrolyte balance, renal failure, and thrombosis. The risk factors associated with ovarian hyperstimulation syndrome are: ① ovaries highly sensitive to ovulatory drugs (hypersensitive ovaries), commonly in patients with polycystic ovaries and young (age <35 years) thin individuals; ② use of HCG to promote ovulation or maintain the corpus luteum of pregnancy; ③ endogenous HCG secretion during early pregnancy; ④ previous history of ovarian hyperstimulation syndrome. In addition, the long-term risks of ovulation promotion drugs are unknown. There are different opinions on whether ovulation promotion drugs increase the long-term cancer risk of patients, but the relevant follow-up studies have not seen a significant increase in the risk of ovarian cancer, breast cancer, or endometrial cancer since the 1960s when mild ovulation promotion regimens were used.