**4. Conventional treatments and limitations**

Assisted reproductive technology (ART), such as artificial insemination (AI), *in vitro* fertiliza‐ tion and embryo transfer (IVF‐ET), and intracytoplasmic sperm injection (ICSI), is responsible for up to 4% of infants born in developing countries.

ART has several iatrogenic complications including the risk of multiples, low luteal phase insufficiency, disabled embryo implantation, ovarian hyperstimulation syndrome (OHSS), and other perinatal and long‐term health conditions [37]. Furthermore, fertility treatments, especially IVF‐ET and ICSI, are costly and risky [38].

Intra‐uterine insemination (IUI), one form of AI, is a commonly used fertility treatment for couples with cervical factor infertility, unexplained subfertility, and subfertility in women with endometriosis after surgical resection [39]. IUI is more useful in some types of severe sex‐ ual dysfunction such a severe ejaculatory dysfunction or vaginismus; in cases of cervical factor or mild male factor infertility; and to prevent the transmission of sexually transmitted diseases such as hepatitis B/C virus (HBV/HCV) and human immunodeficiency virus (HIV) [40].

It is a relatively simple surgical procedure whereby semen that has been washed in the labo‐ ratory is inserted into the uterine cavity by using a small catheter at the time of ovulation. IUI allows sperm to bypass the potentially hostile cervix, and thus increases the number of sperm that reach the uterine cavity and oocyte [40]. The technique can be performed either with or without added medications to encourage ovarian hyperstimulation (OH). In the latter method, follicular growth is monitored either via regular ultrasound monitoring to visualize the follicles or by measuring the preovulatory luteinizing hormone level rise in the serum or urine. In the former, ovulation is induced by an injection of human chorionic gonadotropin (hCG). Timed intercourse (TI), a less invasive method than IUI, involves giving couples infor‐ mation about cycle monitoring so that they can time intercourse appropriately.

Nevertheless, a systematic review revealed that there is no difference in live birth or multiple pregnancy rates in most couples with unexplained subfertility treated with either IUI or TI, both with and without OH [39].
