Unexplained infertility accounts for 10% to 26% of the incidence of infertility and may involve both men and women, and because the cause is unknown, treatment is confusing. We generally recommend a comprehensive analysis of multiple factors such as different ages, years of infertility, and ovarian function of the patient-couple, and use different treatment strategies. This is usually done in three steps: ovulation induction, artificial insemination, and in vitro fertilization. Because of unknown reasons, it is also important to be aware of the risk of IVF fertilization failure in IVF. Couples who have had normal sexual intercourse without contraception for at least 12 months without pregnancy are said to be infertile. Unexplained infertility is a diagnosis of exclusion, which usually means that no abnormality is detected by routine infertility tests, including ovulation in the female partner, no abnormality is detected by gynecological examination and tubal examination, and the male partner’s semen examination is normal, but the infertility is not detected. In other words, no cause related to infertility is found after standardized examination of both partners. Diagnosis of unexplained infertility: unexplained infertility accounts for 10 to 26% of infertility cases. In these seemingly normal couples, the cause of infertility can be complex. Some of these couples really have no problem and the infertility is only delayed, mostly related to age; while other couples with seemingly “normal” infertility tests may have underlying causes that cannot be detected and verified by current routine tests. It has been suggested that hysteroscopic surgery can clearly diagnose pelvic and uterine pathologies, such as pelvic endometriosis and pelvic adhesions, in patients with unexplained infertility, which is useful for clinicians to choose a treatment plan. Unexplained infertility is a provisional and subjective diagnosis, the incidence of which will likely decrease gradually as diagnostic techniques advance. How should unexplained infertility be treated? First of all, a correct understanding of unexplained infertility is needed, and pregnancy-related health counseling should be given, such as quitting smoking, reducing weight, and improving existing bad habits. Couples who are young and have been infertile for a short period of time should be given sufficient time to wait, usually at least 2 years. Three years of infertility is a reasonable period to start treatment and, in addition, patients should realize that natural pregnancy can occur at any time. For young couples with unexplained infertility with normal ovarian function, a “three-step process” can be tried. If the infertile couple is older, has been infertile for a long time, and has declining ovarian function, waiting for a long time is not beneficial and the use of artificial fertility techniques is a reasonable treatment. The recommended drugs and protocols are low-dose gonadotropin, letrozole, or letrozole + low-dose gonadotropin for 3 to 6 cycles, with the goal of single follicle development. 2. Ovulation induction plus intrauterine insemination (IUI): 3-6 cycles of ovulation induction plus intrauterine insemination (IUI) are recommended for those younger than 38 years old with a history of infertility of more than 3 years and normal ovarian function. Ovulation induction drugs and protocols can be letrozole, or letrozole + low-dose gonadotropins. Natural cycles of IUI alone in couples with unexplained infertility do not improve pregnancy rates, and the use of ovulation induction protocols in conjunction with them can increase the chances of pregnancy. Some data show that the cumulative pregnancy rate over 3 cycles can reach up to about 35%, which is higher than the pregnancy rate with either IUI alone or ovulation induction alone. 3. In vitro fertilization and embryo transfer: If ovulation induction plus IUI treatment lasting for more than 3-6 cycles is still unsuccessful, it means that pregnancy is no longer very optimistic. Therefore, a treatment plan using in vitro fertilization (IVF) should be considered. The pregnancy rate per cycle with IVF treatment for unexplained infertility is about 35% to 40%. In addition, in vitro fertilization can diagnose some of the causes of unexplained infertility, such as defective egg maturation, fertilization disorders, and embryo developmental block. Approximately 15-30% of patients with unexplained infertility may present with no or low fertilization, and in primary infertile couples there can be an 11-22% risk of complete fertilization failure. Some patients can achieve higher pregnancy rates by switching to single sperm intracytoplasmic injection (ICSI) in subsequent cycles. Although ICSI significantly improves fertilization rates and reduces the risk of complete fertilization failure. However, the rate of high-quality embryos in the ICSI group of patients with unexplained infertility is not significantly different from that of the IVF group, and it is unclear whether ICSI causes adverse effects on the offspring. Therefore, the choice of fertilization method for patients with unexplained infertility should not be based on blind pursuit of fertilization rate without considering the potential risk of ICSI on the safety of the offspring. It is not recommended to perform ICSI for all patients with unexplained infertility in order to avoid complete failure of fertilization. In conclusion, I hope you will maintain a good lifestyle, relax and cooperate with the relevant examination and treatment chosen for you by your doctor, and I believe you will get pregnant!