Pharmacological Treatments for Infertility

Clinical infertility is a prevalent problem with significant financial and psychosocial costs. In recent years, there is increased awareness to integrate infertility prevention, care and treatment into the basic healthcare services. Management of infertility involves diagnosis, understanding the cause, duration of infertility and the age of male and female. The treatment of infertility is empirical with consideration of efficacy, safety, cost and risks of each treatment option. 

Patients attempting to conceive naturally or through assisted reproduction technologies are advised to follow healthy diet (including folic acid supplementation of 400 μg/day), quit smoking, and reduce caffeine and alcohol consumption. Additionally, weight loss and exercise are also advised for overweight or obese women. Ovulation is profoundly affected by weight, as menstrual cycles are dependent on body mass index. Weight reduction improves menstrual function as a result of increased insulin sensitivity resulting in spontaneous ovulation. Many other different treatment modalities widely used are expectant management, treatment with drugs, and assisted reproduction technologies (ARTs).  

Drugs used to stimulate ovulation include clomiphene citrate, aromatase inhibitors and gonadotropins. Clomiphene citrate exhibit selective antagonistic effect by binding estrogen receptors in hypothalamus, increasing the levels of luteinizing and follicle stimulating hormones thereby stimulating follicular growth and ovulation. Letrozole and anastrazole are third – generation aromatase inhibitors used for ovulation induction, cause reduction in estrogen levels by inhibiting aromatase enzyme. This leads to increased gonadotropin secretion, which stimulates follicular development. Gonadotropins are also used for ovulation induction. However, gonadotropin treatment is more expensive, time consuming, requires intensive monitoring, and has many complications. Metformin, most frequently used insulin-sensitizing agent, is an oral hypoglycemic agent which increases glucose uptake in peripheral tissues, and decreases intestinal glucose absorption and liver glucose production. However, metformin is not approved by the U.S. Food and Drug Administration as an ovulation inducer.  

ARTs include intrauterine insemination (IUI), in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI). IUI is widely used in cases of infertility before resorting to more invasive options like IVF. It involves placement of washed sperms into the uterine cavity around the time of ovulation. IVF involves aspiration of oocytes from follicles immediately before ovulation, followed by fertilization in vitro with sperms from ejaculated semen or surgically extracted in severely oligospermic men. When the embryos reach the morula and blastocyst stages, they are transferred to the uterus for implantation. ICSI, the more robust insemination is used when infertility is associated with sperm related problem. The technique involves injection of a single sperm into mature egg. 

References
1. Soto, E., Copperman, A.B., 2011. Factors Affecting Fertility. In, Seli, E. Eds. Infertility. Series- Gynecology in Practice. Blackwell Publishing ltd., UK. 
2. Nandi, A., Homburg, R., 2016. Unexplained subfertility: diagnosis and management.  The Obstetrician & Gynaecologist. 18, 107-115. 
3. Buckett, W., Sierra, S., 2019. The management of unexplained infertility: an evidence-based guideline from the Canadian Fertility and Andrology Society. RBMO. 39, 4, 633-640. 
4.  Richards, J.S., 2018. Ovulation. Encyclopedia of Reproduction. Reference Module in Biomedical Sciences.Ed.2, 2, 92-98