Correlation of Pregnancy-Associated Plasma Protein (PAPP-A) in Serum and Follicular Fluid with Oocyte and Embryo Quality in PCOS and non-PCOS Women Undergoing ICSI Cycle

Pregnancy-Associated Plasma Protein (PAPP-A) is a zinc metalloproteinase in the insulin growth factor system (IGFs) produced by the syncytiotrophoplast region of the placenta. It plays a critical function in the cleavage of IGFBP4. In the ovary IGFs, it regulates follicular and oocyte maturation, and steroidogenesis. While in polycystic ovarian syndrome (PCOS) Hyperinsulinemia and hyperandrogenemia it causes follicular environment changes and early ovulation resulting in lower oocyte and embryo quality in patients and this will decrease the success of pregnancy in women enrolled in the ICSI cycle. The present study aimed to assess the relationship of PAPP-A levels in serum and follicular fluid in women with PCOS and non-PCOS with oocyte and embryo quality in women undergoing ICSI cycle. 45 infertile Iraqi women were enrolled. Women with PCOS had to meet at least two of the three criteria set by the Rotterdam ESHRE/ASRMS criteria, the age of the included women ranged between 20-45 years. In non-PCOS patients, PAPP-A has higher level in serum and follicular fluid but without a statistically significant difference matching with PCOS group. In addition, there was no significant correlation between PAPP-A levels in serum and follicular fluid with oocytes and embryo characteristics. However, PAPP-A levels are higher in serum and follicular fluid in women with positive pregnancy but without significant differences. PAPP-A had no correlation with oocyte and embryo quality.


Pregnancy-Associated Plasma Protein (PAPP-A) is a zinc
metalloproteinase in the insulin growth factor system (IGFs) produced by the syncytiotrophoplast region of the placenta. It plays a critical function in the cleavage of IGFBP4. In the ovary IGFs, it regulates follicular and oocyte maturation, and steroidogenesis. While in polycystic ovarian syndrome (PCOS) Hyperinsulinemia and hyperandrogenemia it causes follicular environment changes and early ovulation resulting in lower oocyte and embryo quality in patients and this will decrease the success of pregnancy in women enrolled in the ICSI cycle. The present study aimed to assess the relationship of PAPP-A levels in serum and follicular fluid in women with PCOS and non-PCOS with oocyte and embryo quality in women undergoing ICSI cycle. 45 infertile Iraqi women were enrolled. Women with PCOS had to meet at least two of the three criteria set by the Rotterdam ESHRE/ASRMS criteria, the age of the included women ranged between 20-45 years. In non-PCOS patients, PAPP-A has higher level in serum and follicular fluid but without a statistically significant difference matching with PCOS group. In addition, there was no significant correlation between PAPP-A levels in serum and follicular fluid with oocytes and embryo characteristics. However, PAPP-A levels are higher in serum and follicular fluid in women with positive pregnancy but without significant differences. PAPP-A had no correlation with oocyte and embryo quality.

Introduction
Infertility is one of the most frequent health problems in the world, resulting from genetic or pathological diseases, prompting ongoing research and studies in the field of assisted reproductive technology (ART) to find the best treatment options possible (Mongkolchaipak, S [1] ). Despite the efforts of fertility clinics worldwide in the field of ART, there are an estimated 13% of couples influenced by infertility. Therefore, a successful pregnancy needs high-quality oocytes and embryos (Chen, et al. [2] ). Polycystic Ovarian Syndrome (PCOS) is the most frequent endocrine condition and the predominant cause of female infertility, according to studies conducted around the world (Deshpande and Gupta [3] ). PCOS, affects 5-15 % of women and result of ovulatory failure (Ecklund and Usadi [4] ). The clinical expression varies widely but commonly includes oligoanovulation or anovulation, hyperandrogenism (either clinical or biochemical), and the presence of polycystic ovaries on ultrasonography (Fauser,et al. [5] [7] , Öztürk, et al. [8] ). This study is going to assess the correlation between PAPP-A levels and oocyte and embryo characteristics in serum and follicular fluid of women undergoing Intracytoplasmic Sperm Injection (ICSI) cycle.

Materials and Methods
This study involved 45 infertile females who were enrolled in assisted reproductive

Statistical Analysis
The data were investigated using Statistical

Comparison of Hormonal Levels Between PCOS and non-PCOS Groups
The comparison of hormonal levels between PCOS and non-PCOS groups were established in

Comparison of Pregnancy-Associated Plasma Protein Between PCOS and non-PCOS Patients
In the current study, at the day of oocytes

Relationships Between Serum and Follicular PAPP-A Levels with Oocytes and Embryo Characteristics
The relationships between serum PAPP-A levels with patients' oocytes characteristics, and embryos characteristics were shown in Table 4 and Table 5 and the results also revealed no significant correlations between PAPP-A levels with all parameters (low Pearson's correlation coefficient and p > 0.05).

Comparison of Pregnancy-Associated Plasma Protein A (PAPP-A) Levels Between Pregnant and non-Pregnant Patients
The comparison of serum PAPP-A levels between pregnant and non-pregnant patients was presented in Table 6, as a result there was higher serum and follicular fluid PAPP-A levels in women with positive pregnancy but without significant differences between pregnant and non-pregnant (p > 0.05).

Discussion
In the present study, there was no significant showed no significant differences (P > 0.05) between the studied groups. On the other hand, the granulosa cells that surround parenteral and antral follicles produce AMH, which plays a crucial role in follicle growth and maturation.
AMH serum levels have been proposed as a marker for PCOS in several investigations (Bako, et al. [9] ). The current study presented a significant difference in AMH levels (p=0.008) between the PCOS and non-PCOS groups at the day of trigger, with higher levels in the PCOS group.      Likewise, as (Wiweko, et al. [10] ) proposed there were also statistically significant differences between the PCOS and non-PCOS patient in AMH levels. PAPP-A is a zincbinding metalloproteinase that shows an important role in the IGF pathway (Kiliç and Güler [11] , Boldt et al., [12] ). In this study, the level of PAPP-A was compared between the PCOS and non-PCOS groups, and the results presented that non-PCOS patients had higher serum and follicular fluid PAPP-A levels but without statistically significant differences (p > 0.05). While (Wetta, et al. [13] ) showed that women with a PAPP-A value of less than 0.4 MoM were more expected to develop PCOS.
Women with PCOS had a lower PAPP-A level than normal. However, there was no relation between infertility and PAPP-A levels that are less than 0.4 MoM. Although (Öztürk, et al. [8] ) showed that the patients with PCOS revealed higher PAPP-A levels than healthy women, other studies suggested that PAPP-A levels increase throughout a normal pregnancy. There is a sharp increase of about 24-fold between the end of the first trimester and the end of the second trimester, followed by a slower, 2-fold increase from the end of the second trimester up to delivery (Leguy,et al. [14] ). These results reveal that the PAPP-A level increases in pregnant more than in nonpregnant women, mainly in the first trimester. Furthermore

Conclusions
From this study, it was concluded that the

Dr. Amal A. Mohammed
She works at the High Institute of

Infertility Diagnosis and Assisted
Reproductive Technologies, Al Nahrain University, Baghdad, Iraq.