Statistical analysis was conducted using Excel 2013 and SPSS software (version 25; SPSSInc., Chicago, IL, United States). Continuous variables are shown as mean ± standard deviation. Categorical variables are presented as numbers and percentages. Demographic and prescription information was grouped into counts.

According to the inclusion and exclusion criteria standard, we included the prescription data of 225225 patients in the project and analyzed relevant information, such as geography, reimbursement method, expenses, etc. The top three cities where the patients from are Guangzhou (47.83%), Shanghai (19.84%) and Zhengzhou (9.36%). The average age in 5 years is 32.99. The 25-to-34-year-old age range accounts for 60.38% of the entire age range, the largest proportion. The demographic characteristics of specific patients are detailed in Table 1.

We counted the main therapeutic drugs taken by each patient and discovered that they were mainly hormone drugs. There are 11 kinds of primary therapeutic medicines employed. The top five are urotropin for injection (47932, 21.28%), progesterone soft capsules (47472, 21.08%), chorionic gonadotropin for injection (38932, 17.29%), dydrogesterone tables (33591, 14.91%) and triptorelin for injection (26959, 11.97%). See Table 2 for details.

There are three kinds of gonadotropin releasing hormone analogues, two different types of gonadotropin and progesterone, and one type of aromatase inhibitor, anti-estrogen drugs, growth hormone and dopamine agonist drugs respectively. Refer to Figure 1 for a breakdown of the distribution of corresponding types. The total dosage of urotropin ranked first, followed by progesterone. However, the dosage of urotropin and chorionic gonadotropin decreased during 5 years, with urotropin decreasing the most; the dosage of progesterone and didroxyprogesterone increased, with progesterone increasing the most. Figure 2 shows the corresponding trend change diagram.

When summarizing the data, we found that the drug dosage in the clinical drug treatment scheme for infertility is more flexible and changeable. Although the overall drug selection will be similar, the scheme choice differs in different regions or hospitals. For example, the most common usage and dosage of urotropin for injection is 5,000–10000 units at a time (19598, 50.60%). The second most common is to inject 1,000–3,000 IU each time within 9 days after ovulation or embryo transfer (such as on the 3rd, 6th, and 9th days after ovulation induction) (7,916, accounting for 20.33%). Cashmere gonadotropin for injection is used daily starting (or from the fifth day of the cycle) once 75–150 IU. Seven days later, the dose will be adjusted according to the estrogen level and follicular development, and increased to 150–225 IU per day (20901, accounting for 43.61%). Triptorelin for injection once a day accounted for 91.61%, with 0.1 mg and 3.75 mg being the immense proportions, with 6,956 (25.80%) and 5,989 (22.22%) patients, respectively. Take one tablet of didroxyprogesterone twice a day for habitual abortion with a total of 20,600 (accounting for 61.33%) when used for luteal support in assisted reproductive technology. When treating infertility caused by insufficient endogenous progesterone, one tablet of didroxyprogesterone is given orally three times a day for a total of 3,587 (10.68%) tablets. 675 (accounting for 2.01%) take one tablet orally daily on the 14th–25th days of the menstrual cycle. The use of progesterone was divided into oral, injection and suppository, which were 26239 (55.27%), 17002 (35.81%) and 4,231 (8.91%) respectively.

We counted the total and per capita cost of patients using different therapeutic drugs. Triptorelin, urotropin, progesterone, didroxyprogesterone, and leuprorelin were the top five expensive medications. The top five drug expenses per capita for patients receiving complete treatment are goserelin, leuprorelin, triprelin, growth hormone, and didroxyprogesterone. See Table 3 for details.

According to statistics data, the primary age group of infertility treatment locates between 25 and 34, with an average age of 32.99. There has been no substantial increase in the average age of treatment over the past 5 years, and the change in age is not statistically significant (p > 0.05), contrary to the belief of some research that the prevalence of infertility steadily increases with age (Meng, 2014; Sun et al., 2017). The number of patients seeking medical treatment has not increased over the previous 5 years, indicating that the patients’ reproductive demands are mainly concentrated around the age of 33, with the lowest number in 2020. Beyond this age, they give up the focus on breeding offspring, which may be related to the decline of fertility caused by the change in global population structure, environmental pollution and reproductive tract infection. The prevalence of infertility in China appears to be on the rise, although Hu Baoshan and others believe it has remained steady at 25% in recent years (Zhou et al., 2018; Liang et al., 2021), and the number of people treated has not increased. The prevalence of infertility in China looks to be on the rise. However, Hu Baoshan and others believe it has remained stable at 25% in recent years, and the number of individuals receiving treatment has not increased proportionately. Reasons such as the evolution of society, environmental pollution, increased job pressure, delayed marriage and childbearing age, and the number of persons with infertility certificates contribute to a progressive increase in the childbearing age adjustment. Likewise, people’s thoughts are continually evolving and improving.

Guangzhou has the highest proportion of patients. Relevant studies suggest that the infertility prevalence rate of 19,595 first married couples sampled from the population in Guangdong Province from 2002 to 2003 is 14.7% (Hu et al., 2004), which is higher than that of other provinces and cities in China (Zhou et al., 2018; Liang et al., 2021). However, there are other explanations for the varying fraction of infertility treatment patients, including varying diagnostic criteria for infertility, inconsistencies in the precision of calculations, and genuine regional variations in prevalence rates. No conclusion could be drawn from this investigation. Numerous women believe that their age is crucial in determining their fertility. When they reach a particular age, they must resolve any fertility issues. It will become a significant concern if they deviate from this age norm and experience infertility. The rising opportunity cost of women’s motherhood has significantly impeded their childbearing intentions.

In the statistics of outpatient drugs in key cities in China, the varieties and proportion of injections are the most, including the most common ovulation promotion and urinary stimulation, triptorelin, and progesterone. In addition to oral preparations, injection preparations have become the leading drugs in infertility clinics. Both urinary gonadotropin for injection and chorionic gonadotropin for injection belong to gonadotropin. They are often combined with primary or secondary amenorrhea caused by insufficient secretion of gonadotropin and infertility caused by anovulation; Progesterone is generally used to treat functional disorders caused by progesterone deficiency and is also helpful for pregnancy. Progesterone is used in the most multiple ways; Didroxyprogesterone tablets are used to treat diseases caused by endogenous progesterone deficiency, threatened abortion or habitual abortion caused by progesterone deficiency, and infertility caused by corpus luteum deficiency; Triptorelin for injection is mainly used to reduce the serum concentration of sex steroids to the castration level, such as in hormone-dependent prostate cancer, endometriosis, hysteromyoma, etc.

The statistical material of this study differs slightly from that of earlier research. It has been stated that clomiphene (CC) is the most often utilized medication for inducing ovulation (Zegers-Hochschild et al., 2017). Although clomiphene or gonadotropins are problematic due to ovarian hyperstimulation syndrome and multiple pregnancies, which increase the risk of premature birth, and the rate and expense of related neonatal incidence, they are empirical ovarian stimulation methods, according to numerous sources (Practice Committee of American Society for Reproductive Medicine, 2012; Brown and Farquhar., 2016; Lu, 2019; Bansal et al., 2021). Ragni et al. (2012) compared the randomized controlled non-inferiority test of clomiphene citrate and high-dose gonadotropin in vitro fertilization of women with impaired ovarian reserve. It showed that in women with impaired ovarian reserve selected for in vitro fertilization, ovarian stimulation with clomiphene citrate or high-dose gonadotropin could lead to similar pregnancy opportunities, but the cost of the former strategy is lower (Kulkarni et al., 2013). In a study that recruited couples with unexplained infertility in a multicenter, randomized trial, Diamond proposed stimulating the ovary with triazole to reduce multiple pregnancies while maintaining a live birth rate compared with gonadotropin or clomiphene citrate (Ragni et al., 2012).

Clomiphene has been the first-line oral therapy for ovarian stimulation in unexplained infertility for over four decades. Clomiphene is a safe and effective oral medicine. However, it is known to cause pervasive side effects, such as anti-estrogen endometrial and anti-cervical mucus, which may diminish the likelihood of conception. Moreover, clomiphene citrate increases the likelihood of multiple pregnancies compared to natural cycles. These drawbacks are primarily attributable to the extended antiestrogenic impact of accumulated clomiphene in the body (the half-life of clomiphene isomer is several days to several weeks) (Sakhavar et al., 2014; Diamond et al., 2015).

There is no direct data about the effect of luteal phase support on fertility enhancement in spontaneous or non-gonadotropin-induced ovulation cycles. Contrariwise, luteal phase deficit is always present in gonadotropin in vitro fertilization (IVF) and non-IVF cycles, and progesterone has substantial benefits in reproductive results. Due to its extensive and empirical use from the natural ovulation cycle to assisted reproductive technology, the role of progesterone in promoting the luteal phase remains contentious (Chaudhury et al., 2013; Haas and Ramsey, 2013; Pickar, 2018).

Although gonadotropin or clomiphene citrate is currently considered the first-line program for ovulation induction, our survey results indicate that clomiphene is not physicians’ first choice, which may be related to its efficacy and adverse effects. Although progesterone is not a standard recommendation, the dosage of progesterone in different dosage forms is high due to the conventional thinking mode. There was no significant difference in the overall incidence of congenital malformations among children born to mothers who were naturally conceived or treated with letrozole or clomiphene (Miralpeix et al., 2014). Letrozole is extensively recommended for the treatment of breast cancer in postmenopausal women. Recent evidence indicates that letrozole is an effective ovulation-inducing medication (Sharma et al., 2014). Although the proportion of letrozole in this study is not high, the dosage tends to rise.

Sex hormones are flexible in the treatment of infertility. First-line drugs, especially cashmere gonadotropin and urotropin, are the top five drugs with high dosages. Progesterone oral preparation accounted for the highest proportion, followed by injection and suppository dosage form. Progesterone has variable pharmacokinetic and pharmacodynamic features and relative benefits and merits due to different administration routes (Piette, 2020). A preliminary meta-analysis showed no significant difference in the treatment results of vaginal and intramuscular progesterone (Palomba et al., 2015).

Regarding progesterone dosage, a Cochrane analysis revealed that the standard (90 mg/day) or high (equivalent to or greater than 100 mg/day) vaginal progesterone dose was not diverse in the studies (Zarutskie and Phillips, 2009). Less than 300 mg/day of vaginal progesterone is less effective than 100 mg/day of intramuscular progesterone, however there is no difference in efficacy at 600 mg/day (Yanushpolsky, 2015). Oral administration constitutes the most significant proportion in this study, which may be attributable to its convenience. Currently, most scientific information is derived from meta-analyses of observational research and a few randomized controlled trials. Future considerations should include implementing randomized trials and examining the promising efficacy of high-dose subcutaneous progesterone. Gonadotropin-releasing hormone (GnRH) agonists should be utilized to initiate a fresh cycle of multiple ovulation during controlled ovarian hyperstimulation (COH). There is a scientific disagreement about progesterone administration scheme, particularly the route, dose, and timing of administration, as well as the potential interactions with other medicines, which require additional investigation.

The highest amount of drugs used for ovulation induction in IVF clinic is triptorelin, urotropin and progesterone. The top per capita costs are goserelin, leuprorelin, triptorelin and growth hormone. GnRHa drugs have the highest per capita costs. Most ovulation-inducing medications and GnRHa sex hormone therapies, which are utilized for treatment prior to ovulation induction, are among the top-selling pharmaceuticals. Progesterone injection is an essential national drug. Compared with other progesterone preparations, the price is very low, but the use frequency is also very high. The amount of outpatient medication in IVF is obviously out of sync with DDDs. Because IVF is high-tech, the ovulation inducing drugs used are relatively new and the price is relatively high. There is a certain tendency of drug use in the research data of different years. The change of amount in different years and the drug consumption structure show that the drug use in hospitals in different regions is consistent. It shows that everyone generally agrees with the choice of main therapeutic drugs.