Assessment of Cortisol Hormonal Level and Relation with Age in Infertile Women With ICSI Outcome

In human-assisted reproduction both partners need to be evaluated during counseling because causes of infertility are due to male factors and female factors. some body hormones play important role in fertile women and cortisol one of these hormones which is essential for normal ovulation, cortisol usually increases during the follicular phase of the menstrual cycle, play a role in the early stages of follicular development by their interaction with aromatase activity and granulose cell functions. To investigate the correlation of cortisol hormonal level in serum and in follicular fluid that relationship with age in women under Intracytoplasmic sperm injection outcome. Its randomized prospective clinical trial study performance conducting in the Higher Institute for Infertility Diagnosis and Assisted Reproductive Technologies / Al-Nahrain University, Baghdad-Iraq, during the period from November2021to June 2022. a total of Sixty-three Infertile Iraqi women, who planned to inter intrasytoplasmic sperm injection program. The blood sample and follicular fluid sample obtained from all infertile women inter intracytoplasmic sperm injection program to measure cortisol hormonal level at specific days of this study. There was increase in cortisol level in women aged between (30-40) years, So there was significant finding between cortisol level and this age group and there was increase in cortisol level in women aged < 30 years at the same day and no significant difference in cortisol level in women age more than 40. Significant differences in cortisol level appear in group of women age between (30-40) years, also the same result appears in group of women age more than > 40 years and no significant differences in cortisol level in women aged < 30. No significant differences in cortisol level in all age women group (30-40) years, <30 years ,and the women age > 40 years.


Introduction
Infertility is the inability to have children.It is a condition in which a couple is unable to effectively conceive a pregnancy following a period of irregular and unprotected sexual intercourse (Ishiura, S and Yoshida, T.,2019 [1]).There are two types of infertility: Primary infertility is when a couple has never been able to conceive.
Secondary infertility: where a women have one or more pregnancies in the past but is having difficulty conceiving again (Olooto et al.,2012 [2]).Fertility falls as women age.Female fertility peaks between the ages of 18 and 24 years after having conceived, carried the pregnancy to term, or miscarriage (Agboola,2004 [3]).While it begins to fall at the age of 27, it lowers at a slightly faster rate after that .-The p-value of E2 with all these age groups was significant differences (p=0.02) as in the result show in Table (1.1).The p-value of all these age groups was no significant (p=-0.078)as in the result show in Table (

Cortisol in Serum and Age
In this study, the estimated of cortisol in serum was done at the day of oocyte retrieval and embryo transfer; the result found there was a significant correlation between serum cortisol and age.
According to the table, explain that's older women (31-40) years having higher cortisol concentrations than younger women <30 years.This result agreement with a similar study done by (Gan, SD. and Patel KR 2013 [17]).Also, many other authors proof the relationship between women's HPA and cortisol levels.While Eleanor (2020) disagreement with the result of a recent study, suggested that the level of cortisol was lower in the > 40 women.

Cortisol in Follicular Fluid and Age
According to table show that there was a significant increase in cortisol level in Folliclestimulating hormone (FSH): This hormone is key to the regular menstrual cycle and helps induce the maturation of eggs in the ovaries.Women who have ovarian function loss have high levels of FSH as the body tries to compensate for the lack of function (Gonçalves et al., 2010 [4]).Luteinizing Hormone (LH): is responsible for the release of the mature egg during ovulation.Most ovulation prediction kits use this hormone as it increases before ovulation (De Souza et al., 2010 [5]).Anti-Mullerian Hormone (AMH) is produced by the ovarian follicles that contain immature oocytes; the levels of this hormone are used to predict the number of oocytes that are remaining in the ovary.Reduced AMH often can point to infertility (Park HJ et al., 2015 [6]).Estrogen is a hormone that supports the regulation and development of primary and secondary sex characteristics and the reproductive system in females.Estrogen dominance is sometimes found responsible for the difficulty in conception (Fisch JD et al.,2008 [7]).Progesterone is a hormone that is vital to maintaining a pregnancy.It helps the uterine lining to thicken to help grow an embryo.Low progesterone levels in a http://doi.org/10.28969/IJEIR.v12.i1.r3.22 et al., Noor 28 woman can lead to miscarriages.Cortisol is a glucocorticoid with many different functions; the free hormone hypothesis appears to fit the observed effects of cortisol well.Although the ovaries lack the enzymes necessary for cortisol manufacture, they do contain glucocorticoid receptors and are impacted by cortisol.Ovarian follicles control the biological action of the hormone cortisol (Yding Andersen et al. 2002 [8]), Causes of Hormonal Imbalance That Can Lead to Infertility The most common cause of hormonal imbalances that can cause infertility or difficulty in getting pregnant is Anovulation; this is a condition where a woman does not ovulate-polycystic ovarian syndrome.In PCOS, the woman has a hormonal disorder that causes the oocyte to stay immature and turns them into cysts.This can often cause difficulty in getting pregnant and can also cause infertility (Jones, MR et al., 2016 [9]; El Hayek et al., 2016 [10]; Barbieri RL, 2017 [11]; Alzaidi, Z et al., 2021 [12]) Hyperprolactinemia, in this condition, the woman has an excess of prolactin in their body.This causes them to have irregular periods and infertility (Vilar L et al. 2018 [13]) Hypercortisolism which occurs when the body is subjected repeatedly to excessive cortisol levels.There are two types of ACTH-dependent and ACTHindependent causes of Cushing syndrome (Raff H. and Carroll T.,2015 [14]) Hypocortisolism, the most common cause of Autoimmune adrenalitis, is the major cause of primary adrenal insufficiency, often known as Addison disease (Michels A. and Michels N.,2015 [15]).Other potential reasons include malignancy, infection, or adrenal hemorrhage Age and Cortisol in Serum at Embryo Transfer: < 30 years, women which have mean and stander deviation (of 12.55±8.36),(30-40) years, women which have mean and stander deviation (of 13.78±9.03)and > 40 years, women http://doi.org/10.28969/IJEIR.v12.i1.r3.22 et al., Noor 32 which have mean and stander deviation (10.50±6.66) follicular fluid at the day of oocyte retrieval with age groups ranging between (31 -40) years and >40 years, While there was a non-significant change in cortisol level in group aging <30.However, all these results correlated with age was in agreement with (Semman et al., 1994 [18]; Nicolson et al.,1997 [19]).These authors observed an increase in cortisol concentrations in the follicular fluid of older women than young women.

(
Deuschle, M. et al.,1997 [20]) Shows a weak inverse correlation of follicular fluid cortisol level with patient women's age-these finding disagreement with the result of the current study.Conclusion There was a significant increase in cortisol hormonal levels in serum and in follicular fluid in infertile women within the ages 30-40 years and more than 40 years.There was a significant increase in cortisol hormonal levels in blood serum at the day of embryo http://doi.org/10.28969/IJEIR.v12.i1.r3.22 et al., Noor 34 transfer in infertile women that entered the ICSI program.

Estimation of Cortisol, E2 Level in Serum and Cortisol in Follicular Fluid Its Relationship with the Age, the Age that Have Been Divided in this Study into A, B, C
http://doi.org/10.28969/IJEIR.v12.i1.