Decline in fertility of women starts at the age of 30 years old and reach its peak between 40-41. However, disease such as hypogonadism hypogonadotrophic, hyper proloactinemia, cystic fibrosis, systematic diseases, infections, poly cystic ovary (PCO), and premature menopause can impact female fertility. (25) It is said that fertility in women decreases 5% yearly and 3 years of no pregnancy without medical treatment has poor prognosis. Couples with one successful pregnancy has good prognosis. It is recommended that couples with one-year regular intercourse and no successful conception seek medical care. Furthermore, women over 35 and those with irregular menses or organic pathologies such as endometriosis should be evaluated sooner than general population. (8)
Regarding evaluation of infertility in couples, semen analysis is the first step. For women older than 35, ovulatory reserve analysis is crucial by the means of measuring FSH, Inhibin, ALC, and AMH (Anti-müllerian Hormone). Some of the risk factors which impact ovulation reserve are family history of ovarian disease, family history of premature menopause, previous history of chemotherapy and radiotherapy, previous history of ovarian surgery, and smoking. Poor ovarian response can be defined as FSH more than 10 IU/L (more than 18 IU/L has 100% specify), Inhibin less than 40-45, ALC less than 3-4, AMH less than 0.2-0.7, and ovarian volume less than 3cc. Moreover, ovulation factors and hysterosalpingography are done. (14, 26)
Technology and medicine have revolutionized treatments of infertility by the means of IVF. In the process of IVF, gonadotropins are used to increase the rate of oocyte growth and extraction of mature oocytes. Also, they can enhance fertilization of oocyte and successful transferring of fetus in the uterus. (15) The chance of pregnancy is 40-50% in each cycle of IVF. Despite the recent advances in IVF, the chance of fetus implantation and pregnancy is low and the rate of spontaneous abortion and pregnancy failure is considerable. (2, 27) The success of pregnancy by ART is dependent upon age, number and quality of oocytes, and the quality of fetuses. (24) A way to estimate the prognosis of IVF is to evaluate ovarian reserve. Ovarian reserve as the potential of ovaries, reflect the quality and quantity of ovary’s oocytes. There are numerous methods to evaluate ovarian reserve such as checking the ovary volume, number of antral follicles, FSH, and Inhibin B level. (13, 28) AMH (anti-mullerian hormone) has been recently used as a marker for ovarian reserve before administering gonadotropins, since AMH serum level has direct relation to the number of antral follicles. (27)
The number and quality of oocytes produced of ovarian stimulation by gonadotropins affect the success of IVF. To elaborate, poor response to gonadotropins limits the chance of success in IVF which affect 10-15% of women. (12, 28) Previous studies reveal that an ideal result of IVF is a mature oocyte. However, using hormone stimulation is a double-edged sword. Although the production of 5 oocytes considerably decreases the chance of creating a live fetus, producing more than 15 oocytes highly pose the risk of ovarian hyperstimulation syndrome (OHSS). (29) Hence, new methods have been introduced to improve the prognosis of IVF and fertilization naming Royal Jelly.(17) In previous in-vitro studies, Royal Jelly enhanced the maturation and growth of oocytes. Moreover, it positively impacts redux phase and glucose metabolism in cumulus cells. (24, 29) The administration of Royal Jelly showed promising result in maturation of sheep oocytes in in-vivo condition. (16) On the other hand, based on the result of animal studies on male mice, Royal Jelly had protective effect on sperm health against nicotine. They concluded that Royal Jelly by its antioxidant role could protect oocytes as well. (23, 24) Moreover, an animal study done in 2023 on albino female rats, the use of Royal Jelly had protective and anti-oxidant impact against cyclophosphamide induced ovarian damage. (17) In a study in 2019, they claimed that insulin reduce the sensitivity of granulosa follicles to FSH in obese women suffering from obesity. (30) Moreover, insulin resistance is correlated with low quantity of mature oocytes and embryo quality. (10)