Vitamin C supplementation in the patients with endometriosis undergoing in vitro fertilization-embryo transfer

Treatment with Vitamin C via oral administration improves the quality of oocytes and embryos in patients with endometriosis undergoing in vitro fertilization-embryo transfer.

Key Points

Highlights:

• The effect of vitamin C (VitC) supplementation on the outcomes of in vitro fertilization-embryo transfer (IVF-ET) was evaluated by determining the serum and follicular fluid levels of oxidative and anti-oxidative markers and by comparing the treated and non-treated endometriosis group and control group.
• Treatment with VitC via oral route accelerates the level of VitC in serum and follicular fluid improving the quality of oocytes and embryos in IVF-ET cycles.  

Importance:

• The imbalance between oxidative stress and antioxidant capacity affects oocyte and embryo quality adversely.
• The improvement in the oxidative state with VitC changes the results of IVF-ET in patients with endometriosis positively.

 What’s done here?

• This randomized controlled study includes 280 patients with endometriosis who received (n=160) and did not receive (n=120) VitC supplementation and 150 patients without endometriosis undergoing IVF-ET from June 2013 to December 2016.
• Inclusion criteria were <40 years of age with a regular menstrual cycle, a follicle stimulating hormone (FSH) level of <10 IU/L on the 2nd day of the cycle, having >2 years of infertility, requiring infertility treatment by IVF-ET route for the first time.
• Patients with endometriosis complicated by any abnormalities were excluded from the study. Patients with tubal factor undergoing IVF-ET were included as a control group.
• Patients in the study group receiving VitC were randomized in a ratio of 4:3 to receive either 1000 mg VitC per day from 2 months before IVF-ET treatment until 2 weeks after ET or no treatment.
• The long gonadotropin-releasing hormone agonist downregulation protocol during the luteal phase, followed by recombinant FSH injection was administered during the IVF-ET procedure.
• The serum and follicular levels of VitC and oxidative stress markers including superoxide dismutase (SOD), total antioxidant capacity (TAC), malondialdehyde (MAD) and reactive oxygen species (ROS) were evaluated in all patients.
• The fertilization rate, the implantation rate, and clinical pregnancy were evaluated to determine if VitC supplementation affected the outcomes of IVF-ET.        

Key results:

• Of the 160 women with endometriosis receiving VitC, 87 were categorized in stage I and II whereas 73 had stages III and IV. Among the 120 women with endometriosis who have not received VitC, 66 had stages I and II whereas 54 had stages III and IV.    
• IVF-ET and follow-up were successfully performed in 245 patients. VitC, SOD, and TAC in follicular fluid were significantly lower, while their blood levels were slightly lower in patients with endometriosis than in controls.
• The levels of SOD and TAC in follicular fluid were significantly higher than those in blood.
• When VitC at 1000 mg/day was applied, the level of VitC in serum and follicular fluid increased while the markers of oxidative stress (ROS, TAC, SOD, and MDA) did not change.
• Improvement in the serum and follicular levels of VitC ameliorates the quality of oocytes and embryos. However, the fertilization rate, implantation rate, or clinical pregnancy rate did not differ significantly between groups.

Limitations

• The sample size was small. THe patients were not followed-up at different time points (e.g. 2, 4, 6 months) and the patients’ daily diet was not assessed in the study.

Lay Summary

Endometriosis is defined as the localization of endometrial stromal and glandular cells outside the uterine cavity. Women having endometriosis present with dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility. Thus, infertility remains a significant problem for women with endometriosis.

Endometriosis is considered as a complicated chronic inflammatory process associated with an imbalance between oxidative stress and antioxidant response. The role of oxidative stress in the pathogenesis of endometriosis has been the subject of research in recent publications. It has been shown that low levels of several antioxidant components such as VitC, VitA, and VitE in follicular fluid reduce reproductive performance.  Lu et al, a group of scientists from China, published a randomized prospective study titled as “Effects of vitamin C on the outcome of in vitro fertilization–embryo transfer in endometriosis: A randomized controlled study” in the Journal of International Medical Research. These authors investigated whether the VitC administration was beneficial to the outcome of IVF-ET in patients with endometriosis by evaluating the follicular fluid and serum levels of oxidant and antioxidant markers. They administered 1000 mg/day of oral VitC starting from 2 months before IVF-ET treatment until 2 weeks after ET in one group of patients with endometriosis. Another group of patients with endometriosis who did not receive and a third group consisting of women without endometriosis were compared with the endometriosis treatment group. All patients received the long gonadotropin-releasing hormone agonist downregulation protocol, followed by recombinant FSH injection. They were monitored by ultrasound and serum estradiol concentrations. Human chorionic gonadotropin was applied when the size of three leading follicles reached 18 mm in diameter. Fertilization rate was defined as the number of cleavage embryos divided by the number of metaphase II oocytes. Up to 2 embryos were transferred after oocyte pick-up and embryos were assessed using Veeck’s classification. Implantation rate was defined as the number of gestational sacs per transferred embryo, whereas clinical pregnancy was characterized by gestational sac formation in the uterine cavity in serum human chorionic gonadotropin-positive patients. They found that VitC, SOD, and TAC in follicular fluid was significantly lower, while their blood levels were slightly lower in patients with endometriosis than in controls. The levels of SOD and TAC in follicular fluid were significantly higher than those in blood. When VitC at 1000 mg/day was applied, the level of VitC in serum and follicular fluid increased while the markers of oxidative stress (ROS, TAC, SOD, and MDA) did not change. Additionally, they emphasized that the rate of high-grade embryos was higher in the patients with endometriosis receiving VitC.

“The VitC supplementation accelerates the level of VitC in serum and follicular fluid, thereby ameliorating the quality of oocytes and embryos” they added.    

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/30058418