According to World Health Organization (WHO), infertility is a reproduction system disease characterized by failure to achieve a clinical pregnancy after 12 month or more of regular unprotected sexual intercourse. Primary infertility for women is defined by inability to ever bear a child, which can be caused by inability to become pregnant or inability to carry a pregnancy to a live birth. Secondary infertility is when a woman is unable to bear a child after a previous pregnancy or a previous ability to carry a pregnancy to a live birth .
In 2010, 1,9% of 20-44 years old women who seek for a child were unable to attain pregnancy or have a live birth (primary infertility), and 10,5% child-seeking women were unable to have an additional child (secondary infertility). Worldwide, the estimated number of 48,5 million couples are unable to have a child, 21,5 million of which are having primary infertility and the rest are secondary infertility. In the United States, about 6% of married women in reproductive age (15-44 years old) are unable to conceive after a year of regular unprotected sex, and 12% of women 15-44 years old regardless of marital status have difficulty to get pregnant or carry a live birth [2,3].
In Indonesia, according to Riset Kesehatan Dasar (RISKESDAS) 2010, about 5,5-5,9% of married women aged more than 40 years old had not had a living child (primary infertility). This number was even higher in married women aged 20-39, this number varied with the highest was 21,9% .
Infertility is not only women's problems; it can be caused by the male factor. Male factor is responsible in 40% of couples and the female factor is responsible in 40% of couples. The remainder of infertility cases are either male and female factors combined or unexplained infertility, meaning a clear cause is not identified .
Aging is the most common risk factors in infertility, especially among females. Sexually transmitted diseases such as chlamydia and gonorrhea infection is associated with pelvic inflammatory disease, which is a frequent cause for tubal factor infertility. Overweight and obesity in women also associated with ovulatory dysfunction. The most common male factor for infertility is idiopathic, but trauma, infection, varicocele, and exposure to environmental toxin may affect semen production. Smoking in both men and women is also a factor that impairs fertility .
With the development of technology, more advanced treatments for infertility are now available. Infertility can be treated by medication, intrauterine insemination or artificial insemination, and assisted reproductive therapy, including in-vitro fertilization. IVF success rate in United States were quite high, 40% in women younger than 35 years of age, 31% in women aged 35-37 years, 22% in women aged 38-40 years, 12% in women aged 41-42 years, 4% in 43-44 years and 2% in women aged 44 years and older. This number varies from clinic to clinic and also depends on infertility diagnoses .
Despite the availability of infertility treatments, in Indonesia, in-vitro fertilization technique is still not widely used. Based on Indonesia Association for In-Vitro Fertilization (Perfitri) data, in 2010, there were only 2000 cases of in-vitro fertilization in Indonesia, which was only one third of Vietnam's and half of Thailand's. One of the reasons behind this was the service's fee is high, so that low and middle-income family cannot afford it. However, the service's fee varies between clinics. Therefore, new couples with limited budget who have longed for a child could choose cheaper, more affordable clinics if they choose to go for in-vitro fertilization.
We conducted an observational study in two in-vitro fertilization centers in Jakarta. Yasmin Clinic, under Cipto Mangunkusumo General Hospital, offers in-vitro fertilization service with high cost. The other center was Kedoya Clinic, which also offers in-vitro fertilization therapy for lower price. One cycle of in-vitro fertilization in Yasmin Clinic costs 50-70 million rupiahs, depends on initial assessment result and drug used, while in Kedoya Clinic, a cycle of in-vitro fertilization costs 35 million rupiahs. Our primary objective was to evaluate the characteristics of patients and their pregnancy rate following in vitro fertilization in infertile couples who underwent in-vitro fertilization program in these clinics.
2.1. Population and Sample
This is an observational analytic study using retrospective cohort approach. Target population of this research was all infertile couples who underwent in-vitro fertilization treatment. The accessible population was couples who did in-vitro fertilization in Yasmin Clinic (RSCM) and Kedoya Clinic. We used consecutive sampling method to choose the sample used in this study.
2.2. Data Collection
Data from medical record of patients in those two in-vitro fertilization center in Jakarta were collected. All medical records which fulfilled inclusion and exclusion criteria were included in this study. Inclusion criteria used in this research are all infertile couples who opted in-vitro fertilization treatment in Yasmin Clinic or Kedoya Clinic, and who completed the intervention. Data excluded from this study are the ones with incomplete or loss of medical record data.
All medical records from Yasmin Clinic and Kedoya Clinic between October 2014 to September 2015 were collected. From all the collected medical records, 510 met the inclusion and exclusion criteria, 405 of which was from Yasmin Clinic and 105 was from Kedoya Clinic. Indicators used to compare patient's characteristics were maternal age, maternal weight, period of infertility, and paternal age. In-vitro fertilization cycle characteristics were compared using total of in-vitro fertilization trials, number of oocytes, number of inseminated oocytes, embryo produced, fertility rate, cleavage, and cleavage rate. Pregnancy rate in both clinics was assessed with biochemical test after in-vitro fertilization trials.
2.3. Data Analysis
Obtained data then analyzed using Statistical Package for the Social Sciences (SPSS) for Windows version 11.0 software. Statistical analysis used in this paper was Mann-Whitney to compare the characteristics of patients and characteristics of in-vitro fertilization cycle between the centers. Chi-square was used to compare the pregnancy rate between the two clinics based on the biochemical test.
From October 2014 to September 2015, there were 510 complete medical record data which contained biochemical pregnancy. These medical records, 405 data from patients in Yasmin Clinic and 105 data from patients in Kedoya Clinic, were included in the analysis. Data from both clinics showed that there were neither clinical nor statistical difference in maternal weight and infertility duration (Table 1). Even though there were significant statistical difference in paternal and maternal age, there were no clinical difference based on the median. No statistical difference may be caused by large sample size. Overall, there were no significant difference between patients' characteristics in Yasmin Clinic and Kedoya Clinic.
Table 2 showed that there were no significant differences in almost all variables of in-vitro fertilization cycle characteristics. Although total of in-vitro fertilization trials and cleavage rate were statistically significant, they were not clinically significant. Mean difference between number of in-vitro fertilization trials was only 0,22 ± 0,058, and only 1,11 ± 0,840% for cleavage rate. Thus, there were also no significant differences between the two clinics in in-vitro fertilization cycle characteristics.
While patients' characteristics in both clinics were similar, the pregnancy rate in Yasmin Clinic was significantly higher than in Kedoya Clinic, accounted for 64,8% in Yasmin Clinic and 45,7% in Kedoya Clinic (OR = 2,185; 95%CI 1,420-3,361; p=0,001).
Our research shows that there are no characteristic differences in patients of Yasmin Clinic and Kedoya Clinic, in spite of price difference. We expected to see younger patients in Kedoya Clinic as it is cheaper than Yasmin Clinic, but the median showed no age difference in patients of both centers. The reason might be the stigma in community that in-vitro fertilization technique is expensive. Another reason might be that although Kedoya Clinic is cheaper than Yasmin Clinic, the fee is still unaffordable for low- and middle-income family in Indonesia.
Median value of maternal age in both clinics is 34-35 years. Pregnancy in women aged 35 years and older fall into advanced maternal age (AMA) category. Advanced maternal age increases the failure of IVF treatment, risk of maternal near miss, maternal death and severe maternal outcome compared to pregnancy in women aged 20-34 years. It also increases the risk of preterm birth, low birthweight, NICU admission, and birth asphyxia . This finding suggests that the awareness of advanced maternal age is still low, thus selling infertility problem short. Further research may be needed to evaluate maternal educational level towards infertility and advanced maternal age, and education should be given to all young couples about infertility. Young couples should be informed to seek medical attention if they cannot get pregnant after 6 months of regular unprotected intercourse in their early 30s to have a safer, healthier pregnancy.
Despite patients' similar characteristics, pregnancy rate in Yasmin Clinic is significantly higher than in Kedoya Clinic. The pregnancy rate difference implies that there are another factors which are not included in this study, may be patients' compliance, or technical issues such as different in-vitro fertilization technique, different medium used to transfer the embryo, quality of reagents, or technician's skill. It seems that higher cost also increases the effectivity and quality of in-vitro fertilization program, yet another study should be conducted to evaluate these factors.
There are no differences in patients' characteristics in Yasmin Clinic (high cost) and Kedoya Clinic (lower cost), which may be caused by the price is still too high for the society. However, the pregnancy rate is significantly higher in Yasmin Clinic and Kedoya Clinic, suggesting high cost increases the quality of treatment.
Authors would like to thank our mentor, Dr. dr. Budi Wiweko, SpOG(K) for his expertise which guided us in doing this study, helping and supporting us in many ways while making this paper. This research also made possible with cooperation of Yasmin Clinic and Kedoya Clinic for letting us do the research there. We also would like to express our gratitude to all related parties we cannot name one by one, who have encouraged us, gave us insights while doing this research.