Ten years of in vitro fertilization in Indonesia: Access to infertility care in a developing country.

OBJECTIVE: This research was conducted to assess access to assisted reproductive technologies (ART) and the current status of the in vitro fertilization (IVF) program that have been implemented in Indonesia over the last 10 years. METHODS: We established a retrospective cohort study and descriptive analysis of the current state of access to infertility care in Indonesia. The data were collected from all IVF centers, clinics, and hospitals in Indonesia from 2011 to 2020, including the number of IVF clinics, total ART cycles, retrieved fresh and frozen embryos, average age of IVF patients, IVF pregnancy rate, and causes of infertility. RESULTS: The number of reported fertility clinics in Indonesia has increased from 14 clinics in 2011 to 41 clinics by 2020. As many as 69 569 ART cycles were conducted over the past 10 years, of which 51 892 cycles used fresh embryos and 17 677 cycles used frozen embryos. The leading cause of consecutive infertility diagnosis was male infertility. Nearly half of the women who underwent IVF procedures (48.9%) were under 35 years old. The pregnancy rate outcome of women who underwent IVF ranged from 24.6% to 37.3%. CONCLUSION: Developments in ART in Indonesia have led to improvements in the ART cycles performed throughout the 10 year period. The identification of key areas that require improvement can provide an opportunity to enhance access to infertility care.

Positive Correlation of Oestradiol Level on Trigger Day with the Secretion Level of Endometrial Kisspeptin and Leukaemia Inhibitory Factor in the Mid-Luteal Stimulated Cycle.

Background: Kisspeptin plays a role in the oestradiol negative-feedback regulation of GnRH as well as gonadotropin. In addition, kisspeptin has been postulated to induce the production of an important cytokine called leukaemia inhibitory factor (LIF). Aims: This study aims to investigate the correlation between varying oestradiol levels measured on trigger day of the ovarian stimulation and the mRNA expression level of endometrial kisspeptin and LIF. Study Setting and Design: Prospective cross-sectional study took place in Morula IVF Jakarta clinic. Materials and Methods: A total of 43 infertile couples underwent an in-vitro fertilization (IVF) program. Subjects were grouped based on oestradiol levels as follows: group A ([≧ 3000 pg/mL, n = 15], group B [2000-2999 pg/mL, n = 14], group C [<2000 pg/mL, n = 14]). Statistical Analysis Used: ANOVA test was utilised to compare the expression of kisspeptin and LIF among study groups while Pearson correlation was used to identify the correlation between variables. Results: A significantly higher mRNA expression of both Kisspeptin and LIF was found in group A than in groups B and C (P < 0.001). The mRNA expression of kisspeptin and LIF correlated positively with the oestradiol level (r = 0.638, P < 0.001 and r = 0.634, P < 0.001, respectively). Moreover, a strong association between Kisspeptin and LIF expression was also detected (r = 0.700, P < 0.001). Conclusions: mRNA expression of kisspeptin and LIF was significantly different according to the oestradiol levels in the study groups. Increased oestradiol level was shown to elevate the expression of endometrial kisspeptin and LIF in women undergoing the IVF programme.

Role of three-dimensional Doppler ultrasonography and leukemia inhibitory factor from endometrial secretion in predicting endometrial receptivity in IVF treatment: a pilot study.

PURPOSE: This pilot study aimed to evaluate the potential synergistic role of three-dimensional power Doppler angiography ultrasound and the expression of Leukemia Inhibitory Factor (LIF) protein in predicting the endometrial receptivity of fresh In-Vitro Fertilization (IVF) cycles. MATERIALS AND METHODS: This prognostic cohort study involved 29 good prognosis women who underwent fresh IVF cycles with fresh blastocysts transfer. Serial measurements of sub-endometrial parameters including vascularity index (VI), flow index (FI), and vascularization flow index (VFI) were conducted consecutively via power Doppler angiography on the day of oocyte maturation trigger, oocyte retrieval, and blastocyst transfer. Aspiration of endometrial secretion was performed on the day of embryo transfer. RESULTS: The mean index of VI and VFI on the trigger and oocyte retrieval day and also LIF protein concentration at the window of implantation were significantly higher in clinically pregnant women than that of the non-pregnant women (p < 0.05). The area under the curve (AUC) of VI and VFI was shown to have a powerful predictive value to forecast receptive endometrium on either trigger day (0.788 and 0.813, respectively) or oocyte retrieval day (0.813 and 0.818). Likewise, LIF concentration on the day of embryo transfer was adequate to become a predictor for endometrial receptivity (AUC 0.874). A combination of the VI and VFI on the trigger day and LIF concentration at specific cut-off values (VI > 5.381, VFI > 1.483, LIF 703.5 pg/mL) produced an algorithm with high AUC (0.881) and high specificity (94.4%) for an adequate prediction of non-receptive endometrium. CONCLUSION: VI and VFI index assessed on maturation trigger day and the expression of LIF protein concentration at the window of implantation provided sufficient information to predict endometrial receptivity. A large randomized control trial is needed to validate these findings.

Survival of isolated human preantral follicles after vitrification: Analyses of morphology and Fas ligand and caspase-3 mRNA expression.

OBJECTIVE: This study aimed to examine the effect of vitrification on apoptosis and survival in human preantral follicles after thawing. METHODS: This experimental study was conducted at an acute tertiary care hospital from March 2012 to April 2013. Ovaries were sliced into 5×5×1-mm pieces and divided into the following three groups: preantral follicle isolation, ovarian tissue vitrification-warming followed by follicle isolation, and immunohistochemistry of fresh ovarian tissue. For statistical analyses, the Student t-test, chi-square test, Kruskal-Wallis test, and Kaplan-Meier survival analysis were used. RESULTS: A total of 161 preantral follicles (70% secondary) were collected from ovarian cortex tissue of six women between 30 and 37 years of age who underwent oophorectomy due to cervical cancer or breast cancer. There were no significant differences in the follicular morphology of fresh preantral follicles and vitrified follicles after thawing. The mean Fas ligand (FasL) mRNA expression level was 0.43±0.20 (relative to ß-actin) in fresh preantral follicles versus 0.51±0.20 in vitrified follicles (p=0.22). The mean caspase-3 mRNA expression level in fresh preantral follicles was 0.56±0.49 vs. 0.27±0.21 in vitrified follicles (p=0.233). One vitrified-thawed secondary follicle grew and developed to an antral follicle within 6 days of culture. CONCLUSION: Vitrification did not affect preantral follicle morphology or mRNA expression of the apoptosis markers FasL and caspase-3. Further studies are required to establish whether vitrification affects the outcomes of in vitro culture and the maturation of preantral follicles.