The cumulative live birth rate and cost-effectiveness of the clomiphene and gonadotropin cotreatment protocol versus the mid-luteal GnRH agonist protocol in women over 35 years old.

The decrease in assisted reproductive technology success among older women, attributed to decreased oocyte quantity and quality, poses a significant challenge. Currently, no consensus on the optimal ovarian stimulation protocol for older women undergoing IVF exists. This retrospectively registered cohort study aimed to compare the cumulative live birth rate (CLBR), time to live birth (TTLB), and cost-effectiveness among women older than 35 years who were receiving either the gonadotropin-releasing hormone agonist (GnRHa) or clomiphene citrate and gonadotropin cotreatment with ovarian stimulation (CC cotreatment) protocol. To compare treatment outcomes, we performed propensity score matching (PSM) on 2871 IVF cycles in women older than 35 years who received either the GnRHa or CC cotreatment protocol, resulting in 375 cycles in each group. Additionally, a decision tree model was utilized to assess the cost-effectiveness of the two protocols. Following PSM, both groups had similar baseline characteristics. The CC cotreatment protocol resulted in a greater rate of cycle cancellation (13.07% vs. 8.00%, p = 0.032), but the groups maintained comparable fertilization rates and embryo quality. Although the TTLB was longer in the CC cotreatment group, the CLBR per initial cycle (41.07% vs. 45.33%, p = 0.269) and delivery outcomes were similar between the two groups at the 24 months follow-up. Additionally, the average cost per live birth in the CC cotreatment group was 21.27% lower than in the GnRHa group (¥32,301.42 vs. ¥39,174.22). In conclusion, for women older than 35 years undergoing IVF, the CC cotreatment protocol offered a comparable CLBR to the GnRHa protocol but with reduced costs, indicating its potential as a viable and cost-effective ovarian stimulation option.Clinical trial registration: https://www.chictr.org.cn/ , identifier [ChiCTR2300076537].

A randomized controlled trial to evaluate the use of a web-based application to manage medications during in vitro fertilization.

OBJECTIVE: To evaluate the use of a web-based application that assists in medication management during in vitro fertilization (IVF) treatment. DESIGN: Multicenter randomized controlled trial. SETTING: University hospitals. PATIENT(S): Women undergoing IVF. INTERVENTION(S): Subjects were recruited to assess quality of life during IVF and were randomly assigned to use either the OnTrack application to assist with medication management or conventional medication management. Surveys were administered at four time points. MAIN OUTCOME MEASURE(S): Medication surplus, incidence of medication errors, amount of patient-initiated communication, and patient satisfaction. RESULT(S): A total of 153 women participated. The average number of portal messages and telephone calls was similar between groups. Twelve patients in the control group (12/69, 17.4%) and 8 patients in the case group (8/72, 11.1%) made medication errors. There were similar amounts of medication surplus in the two groups. The estimated cost of medication waste was $2,578 ± $2,056 in the control group and $2,554 ± $1,855 in the case group. Patient satisfaction was similar between the two groups. CONCLUSION(S): Use of a web-based application did not decrease medication errors, medication surplus, or patient-initiated messages. Many patients had a medication surplus, which can be an area of cost reduction during IVF. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT03383848.

Cumulative Live Birth Rate and Cost-Effectiveness Analysis of Gonadotropin Releasing Hormone-Antagonist Protocol and Multiple Minimal Ovarian Stimulation in Poor Responders.

Background: The overall cumulative live birth rate (CLBR) of poor ovarian responders (POR) is extremely low. Minimal ovarian stimulation (MOS) provides a relatively realistic solution for ovarian stimulation in POR. Our study aimed to investigate whether multiple MOS strategies resulted in higher CLBR compared to conventional gonadotropin releasing hormone (GnRH) antagonists in POR. Methods: This retrospective study included 699 patients (1,058 cycles) from one center, who fulfilled the Bologna criteria between 2010 and 2018. Overall, 325 women (325 cycles) were treated with one-time conventional GnRH antagonist ovarian stimulation (GnRH-antagonist). Another 374 patients (733 cycles) were treated with multiple MOS including natural cycles. CLBR and time-and-cost-benefit analyses were compared between these two groups of women. Results: GnRH antagonists provided more retrieved oocytes, meiosis II oocytes, fertilized oocytes, and more viable embryos compared to both the first MOS (p < 0.001) and the cumulative corresponding numbers in multiple MOSs (p < 0.001). For the first in vitro fertilization (IVF) cycle, GnRH antagonists resulted in higher CLBR than MOS [12.92 versus 4.54%, adjusted OR (odds ratio) 2.606; 95% CI (confidence interval) 1.386, 4.899, p = 0.003]. The one-time GnRH-antagonist induced comparable CLBR (12.92 versus 7.92%, adjusted OR 1.702; 95% CI 0.971, 2.982, p = 0.063), but a shorter time to live birth [9 (8, 10.75) months versus 11 (9, 14) months, p = 0.014] and similar financial expenditure compared to repeated MOS [20,838 (17,953, 23,422) ¥ versus 21,261.5 (15,892.5, 35,140.25) ¥, p = 0.13]. Conclusion: Both minimal ovarian stimulation (MOS) and GnRH-antagonists provide low chances of live birth in poor responders. The GnRH antagonist protocol is considered a suitable choice for PORs with comparable CLBR, shorter times to live birth, and similar financial expenditure compared to repeated MOS.

Decision analysis about the cost-effectiveness of different in vitro fertilization-embryo transfer protocol under considering governments, hospitals, and patient.

OBJECTIVE: The aim of this study was to explore the benefits of in vitro fertilization (IVF) for patients and hospitals under different protocols and if IVF treatment should be incorporated into health care. PERSPECTIVE: The government should consider including IVF treatment in health insurance. Hospitals and patients could obtain the best benefit by following the hospital's recommended protocol. SETTING: This retrospective study was conducted from January 2014 to August 2017 at an academic hospital. METHODS: A total of 7440 patients used gonadotropin-releasing hormone agonists (GnRHa) protocol, 2619 patients used, gonadotropin-releasing hormone antagonists (GnRHant) protocol, and 1514 patients used GnRHa ultra-long protocol. Primary outcomes were live birth rate (LBR), cost-effectiveness, hospital revenue, and government investment. RESULTS: The cycle times for the GnRHa protocol and the GnRHa ultra-long protocol were significantly higher than the GnRHant protocol. Patients who were ≤29 years chose the GnRHant protocol. The cost of a successful cycle was 67,579.39 ±â€Š9,917.55 ¥ and LBR was 29.25%. Patients who were >30 years had the GnRHa protocol as the dominant strategy, as it was more effective at lower costs and higher LBR. When patients were >30 to ≤34 years, the cost of a successful cycle was 66,556.7 ±â€Š8,448.08 ¥ and the LBR was 31.05%. When patients were >35 years, the cost of a successful cycle was 83,297.92 ±â€Š10,918.05 ¥ and the LBR was 25.07%. The government reimbursement for a cycle ranged between 11,372.12 ±â€Š2,147.71 ¥ and 12,753.67 ±â€Š1,905.02 ¥. CONCLUSIONS: The government should consider including IVF treatment in health insurance. Hospitals recommend the GnRHant protocol for patients <29 years old and the GnRHa protocol for patients >30 years old, to obtain the best benefits. Patients could obtain the best benefit by using the protocol recommended by the hospital.

Cost-effectiveness of elagolix versus leuprolide acetate for treating moderate-to-severe endometriosis pain in the USA.

AIM: To assess the cost-effectiveness of elagolix versus leuprolide acetate in women with moderate to severe endometriosis pain. METHODS: A Markov model was developed. The efficacy of leuprolide acetate was derived from statistical prediction models using elagolix trial data. Model inputs were extracted from Phase III clinical trials and published literature. RESULTS: Compared with leuprolide acetate, elagolix generated positive net monetary benefit (NMB) assuming a payer's willingness-to-pay threshold of US$100,000 per quality-adjusted life year over a 1-year time horizon: US$5660 for elagolix 150 mg and US$6443 for elagolix 200 mg. The 2-year NMBs were also positive. CONCLUSION: Elagolix was cost effective versus leuprolide acetate in the management of moderate to severe endometriosis pain over 1- and 2-year time horizons. Results were robust in sensitivity analyses.

Artificial Cycle with or without a Depot Gonadotropin-releasing Hormone Agonist for Frozen-thawed Embryo Transfer: An Assessment of Infertility Type that Is Most Suitable.

The clinical outcomes of five groups of infertility patients receiving frozen-thawed, cleavage-stage embryo transfers with exogenous hormone protocols with or without a depot gonadotropin-releasing hormone (GnRH) agonist were assessed. A retrospective cohort analysis was performed on 1003 cycles undergoing frozen-thawed, cleavage-stage embryo transfers from January 1, 2012 to June 31, 2015 in the Reproductive Medicine Center of Wuhan General Hospital of Guangzhou Military Region. Based on the infertility etiologies of the patients, the 1003 cycles were divided into five groups: tubal infertility, polycystic ovary syndrome (PCOS), endometriosis, male infertility, and unexplained infertility. The main outcome was the live birth rate. Two groups were set up based on the intervention: group A was given a GnRH agonist with exogenous estrogen and progesterone, and group B (control group) was given exogenous estrogen and progesterone only. The results showed that the baseline serum hormone levels and basic characteristics of the patients were not significantly different between groups A and B. The live birth rates in groups A and B were 41.67% and 29.29%, respectively (P<0.05). The live birth rates in patients with PCOS in groups A and B were 56.25% and 30.61%,respectively (P<0.05). The clinical pregnancy, implantation and on-going pregnancy rates showed the same trends as the live birth rates between groups A and B. The ectopic pregnancy rate was significantly lower in group A than in group B. We concluded that the live birth rate was higher and other clinical outcomes were more satisfactory with GnRH agonist cotreatment than without GnRH agonist co-treatment for frozen-thawed embryo transfer. The GnRH agonist combined with exogenous estrogen and progesterone worked for all types of infertility tested, especially for women with PCOS.

Cost-effectiveness of ovarian stimulation with gonadotrophin and clomiphene citrate in an intrauterine insemination programme for subfertile couples.

Ovarian stimulation with low-dose human menopausal gonadotrophin (HMG) is superior to clomiphene citrate in intrauterine insemination (IUI) cycles with respect to clinical pregnancy rate, but it is unclear whether HMG is also the more cost-effective option. The aim of this study was to compare the cost-effectiveness of ovarian stimulation with low-dose subcutaneously administred HMG (37.5-75 IU per day) to orally administred clomiphene citrate (50 mg/day from day 3-7) in an IUI programme for subfertile couples. A cost-effectiveness analysis was conducted using the results of a randomized trial, including 620 IUI cycles. The primary outcome was the incremental cost-effectiveness ratio (ICER) of using HMG versus clomiphene citrate. Results are presented from the healthcare payer perspective. The total cost per patient associated with one IUI treatment with HMG is €764, whereas it is €558 if clomiphene citrate is used, resulting in an incremental cost of €206 for HMG per treatment. The incremental clinical pregnancy rate of using HMG instead of clomiphene citrate, however, is also 5.7 percentage points higher, resulting in an ICER of HMG versus clomiphene citrate of €3615 per additional clinical pregnancy achieved. On average, HMG was found to be more cost-effective than clomiphene citrate.

Role of Markov Modeling Approaches to Understand the Impact of Infertility Treatments.

We are proposing to use Markov modeling type of analysis to understand data generated by treatments for infertility in women receiving ovarian stimulations. We describe the conceptual novelties, need for such an analysis, basics of the proposed methods, and theoretical constructions of various probabilities associated with practical level implementation of the Markov modeling procedures. This method can be adopted to infertility-related data visualizations whenever progression of outcome stages in infertility treatment is recorded. These methods if implemented should be able to enhance the understanding of treatment impacts of gonadotropins, clomiphene citrate, or an aromatase inhibitor at the beginning of treatment cycles of infertile women. This framework will be very useful for infertility treatment practitioners to compute the values of success rates of treatment for total population or population divided by demographic, clinical, and genetic factors. These methods can be continuously updated with newer data and translated into a mobile app to be used by clinical practitioners.

Cost effectiveness of letrozole and purified urinary FSH in treating women with clomiphene citrate-resistant polycystic ovarian syndrome: a randomized controlled trial.

We aimed to compare the cost effectiveness of letrozole versus purified urinary follicle stimulating hormone (FSH) in treating patients with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). This was a randomized trial conducted in Cairo University and Beni-Suef University Hospitals, Egypt. A cohort of 140 eligible women was randomized to receive either letrozole 2.5 mg twice daily for five days, or FSH using a graduated regimen starting with a dose of 75 IU. Treatment was repeated for three months if pregnancy did not occur. There were no significant differences between the two treatments in the cumulative clinical pregnancy rate (30% vs. 34%; p = 0.578), cumulative ovulation rate (47% vs. 57%; p = 0.236), miscarriage rate (9% vs. 4%, p > 0.999) or multiple pregnancy rate (0% and 8%, p = 0.491) but the FSH cycles were 4.8 times more expensive. Letrozole and FSH were both effective in treating women with CC-resistant PCOS but letrozole was more cost effective.Study registration number: NCT02304107.

Economic Evaluation of Three Frequently Used Gonadotrophins in Assisted Reproduction Techniques in the Management of Infertility in the Netherlands.

BACKGROUND AND OBJECTIVE: Subfertility represents a multidimensional problem associated with significant distress and impaired social well-being. In the Netherlands, an estimated 50,000 couples visit their general practitioner and 30,000 couples seek medical specialist care for subfertility. We conducted an economic evaluation comparing recombinant human follicle-stimulating hormone (follitropin alfa, r-hFSH, Gonal-F®) with two classes of urinary gonadotrophins-highly purified human menopausal gonadotrophin (hp-HMG, Menopur®) and urinary follicle-stimulating hormone (uFSH, Fostimon®)-for ovarian stimulation in women undergoing in vitro fertilization (IVF) treatment in the Netherlands. METHODS: A pharmacoeconomic model was developed, simulating each step in the IVF protocol from the start of therapy until either a live birth, a new IVF treatment cycle or cessation of IVF, following a long down-regulation protocol. A decision tree combined with a Markov model details progress through each health state, including ovum pickup, fresh embryo transfer, up to two subsequent cryo-preserved embryo transfers, and (ongoing) pregnancy or miscarriage. A health insurer perspective was chosen, and the time horizon was set at a maximum of three consecutive treatment cycles, in accordance with Dutch reimbursement policy. Transition probabilities and costing data were derived from a real-world observational outcomes database (from Germany) and official tariff lists (from the Netherlands). Adverse events were considered equal among the comparators and were therefore excluded from the economic analysis. A Monte Carlo simulation of 5000 iterations was undertaken for each strategy to explore uncertainty and to construct uncertainty intervals (UIs). All cost data were valued in 2013 Euros. The model's structure, parameters and assumptions were assessed and confirmed by an external clinician with experience in health economics modelling, to inform on the appropriateness of the outcomes and the applicability of the model in the chosen setting. RESULTS: The mean total treatment costs were estimated as €5664 for follitropin alfa (95 % UI €5167-6151), €5990 for hp-HMG (95 % UI €5498-6488) and €5760 for uFSH (95 % UI €5256-6246). The probability of a live birth was estimated at 36.1 % (95 % UI 27.4-44.3 %), 33.9 % (95 % UI 26.2-41.5 %) and 34.1 % (95 % UI 25.9-41.8 %) for follitropin alfa, hp-HMG and uFSH, respectively. The costs per live birth estimates were €15,674 for follitropin alfa, €17,636 for hp-HMG and €16,878 for uFSH. Probabilistic sensitivity analysis indicated a probability of 72.5 % that follitropin alfa is cost effective at a willingness to pay of €20,000 per live birth. The probabilistic results remained constant under several analyses. CONCLUSION: The present analysis shows that follitropin alfa may represent a cost-effective option in comparison with uFSH and hp-HMG for IVF treatment in the Netherlands healthcare system.

Gonadotropin Therapy versus Laparoscopic Ovarian Drilling in Clomiphene Citrate-Resistant Polycystic Ovary Syndrome Patients: A Retrospective Cost-Effectiveness Analysis.

BACKGROUND: Gonadotropin therapy and laparoscopic ovarian drilling (LOD) are treatment options for ovulation induction (OI) in clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS) patients. The current evidence of the cost-effectiveness of both treatments is scarce, conflicting and performed from different health-economic perspectives. METHODS: A retrospective health-economic evaluation was performed from a societal perspective in which human menopausal gonadotropin (hMG) therapy (n = 43) was compared with LOD (n = 35), followed by OI with CC and/or hMG if spontaneous ovulation did not occur within 2 months. Data were collected until the patients were pregnant, with a time limit of 6 months after the onset of treatment. Outcomes were expressed as ongoing pregnancy rate and number of live-born children. RESULTS: The ongoing pregnancy rate was 21/35 (60%) after LOD and 30/43 (69.8%) after hMG treatment (relative risk 0.85, 95% CI 0.61-1.19). The societal cost per patient, up to an ongoing pregnancy, was significantly higher after LOD versus hMG treatment (adjusted mean difference EUR 1,073, 95% CI 180-1,967). CONCLUSION: This economic evaluation based on real-life data shows that the societal cost up to an ongoing pregnancy is less after hMG treatment when compared with LOD surgery in CC-resistant PCOS patients.

Assessment of multiple intrauterine gestations from ovarian stimulation (AMIGOS) trial: baseline characteristics.

OBJECTIVE: To identify baseline characteristics of women with unexplained infertility to determine whether treatment with an aromatase inhibitor will result in a lower rate of multiple gestations than current standard ovulation induction medications. DESIGN: Randomized, prospective clinical trial. SETTING: Multicenter university-based clinical practices. PATIENT(S): A total of 900 couples with unexplained infertility. INTERVENTION(S): Collection of baseline demographics, blood samples, and ultrasonographic assessments. MAIN OUTCOME MEASURE(S): Demographic, laboratory, imaging, and survey characteristics. RESULT(S): Demographic characteristics of women receiving clomiphene citrate (CC), letrozole, or gonadotropins for ovarian stimulation were very consistent. Their mean age was 32.2 ± 4.4 years and infertility duration was 34.7 ± 25.7 months, with 59% primary infertility. More than one-third of the women were current or past smokers. The mean body mass index (BMI) was 27 and mean antimüllerian hormone level was 2.6; only 11 women (1.3%) had antral follicle counts of <5. Similar observations were identified for hormonal profiles, ultrasound characterization of the ovaries, semen parameters, and quality of life assessments in both male and female partners. CONCLUSION(S): The cause of infertility in the couples recruited to this treatment trial is elusive, as the women were regularly ovulating and had evidence of good ovarian reserve both by basal FSH, antimüllerian hormone levels, and antral follicle counts; the male partners had normal semen parameters. The three treatment groups have common baseline characteristics, thereby providing comparable patient populations for testing the hypothesis that use of letrozole for ovarian stimulation can reduce the rates of multiples from that observed with gonadotropin and CC treatment. CLINICAL TRIAL REGISTRATION NUMBER: NCT 01044862.

Outcomes after intrauterine insemination are independent of provider type.

OBJECTIVE: We sought to determine whether the success of intrauterine insemination (IUI) varies based on the type of health care provider performing the procedure. STUDY DESIGN: This was a retrospective cohort study set at an infertility clinic at an academic institution. The patients who comprised this study were 1575 women who underwent 3475 IUI cycles from late 2003 through early 2012. Cycles were stratified into 3 groups according to the type of provider who performed the procedure: attending physician, fellow physician, or registered nurse (RN). The primary outcome was live birth. Additional outcomes of interest included positive pregnancy test and clinical pregnancy. Repeated measures log binomial regression was used to estimate the risk ratios (RR) and 95% confidence intervals (CI) for the outcomes and to evaluate the effect of potential confounders. All tests were 2-sided, and P values < .05 were considered statistically significant. RESULTS: Of the 3475 IUI cycles, 2030 (58.4%) were gonadotropin stimulated, 929 (26.7%) were clomiphene citrate stimulated, and 516 (14.9%) were natural. The incidences of clinical pregnancy and live birth among all cycles were 11.8% and 8.8%, respectively. After adjusting for female age, male partner age, and cycle type, the incidence of live birth was similar for RNs compared with attending physicians (RR, 0.80; 95% CI, 0.58-1.1) and fellow physicians compared with attending physicians (RR, 0.84; 95% CI, 0.58-1.2). Similar results were seen for positive pregnancy test and clinical pregnancy. CONCLUSION: There was no significant difference in live birth following IUI cycles in which the procedure was performed by a fellow physician or RN compared with an attending physician.

Biological risk versus socio-economic advantage: low birth-weight, multiple births and income variations among Irish infants born following fertility treatments.

The Growing Up in Ireland Infant Cohort dataset (n = 11,134) includes information on fertility treatments for over 400 infants. IVF (28.1 %) and IVF-related treatments (17.8 %) were the most frequent, but there was also a high percentage following clomiphene citrate alone (31.5 %). Infants born following fertility treatment were much more likely to be in higher income families, and this relationship was not accounted for by older mothers in wealthier families. Analysis of fertility-treatment pregnancies among Irish infants, controlling for income and maternal age, shows a greater risk of multiple birth and low birth-weight, although the latter appears to be largely related to the former especially for IVF-type treatments.

Use of fertility treatment modalities in a large United States cohort of professional women.

OBJECTIVE: To evaluate the use of fertility treatments among a large cohort of women in the United States. DESIGN: Cohort study. SETTING: Nurses' Health Study II. PATIENT(S): Ten thousand thirty-six women who reported having used fertility treatment on biennial questionnaires from 1993-2009. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Data on patterns of treatment modality were collected via self-report from validated mailed questionnaires. Information on clomiphene, gonadotropin injections alone, and gonadotropin injections as part of intrauterine insemination (IUI) and in vitro fertilization (IVF) was queried. RESULT(S): Most women who reported fertility treatment used clomiphene (94%), with a large majority reporting clomiphene as their only form of treatment (73%). Of women who reported treatment more advanced than clomiphene, 13% had used gonadotropin injections alone, 11% IUI treatment, and 11% IVF. Several subgroups were more likely to use multiple treatment modalities and to initiate treatment with gonadotropins rather than clomiphene, including women living in states with insurance coverage of fertility procedures, with higher household income, younger in age, who remained nulliparous at the study close, and treated after 2000. CONCLUSION(S): Results should be interpreted cautiously, but to our knowledge, this represents the first study of fertility treatment patterns in the United States and could inform public health planning.

Cost-effectiveness of treatment strategies in women with PCOS who do not conceive after six cycles of clomiphene citrate.

This study evaluated the cost-effectiveness of treatments for women with polycystic ovary syndrome (PCOS) who ovulate on clomiphene citrate but do not conceive after six cycles. A decision-analytic framework was developed for six scenarios: (1) three cycles of IVF; (2) continuation of clomiphene citrate for six cycles, followed by three cycles of IVF in case of no birth; (3) six cycles of gonadotrophins and three cycles of IVF; (4) 12 cycles of gonadotrophins and three cycles of IVF; (5) continuation of clomiphene citrate for six cycles, six cycles of gonadotrophins and three cycles of IVF; (6) continuation of clomiphene citrate for six cycles, 12 cycles of gonadotrophins and three cycles of IVF. Two-year cumulative birth rates were 58%, 74%, 89%, 97%, 93% and 98% and costs per couple were € 9518, € 7530, € 9711, € 9764, € 7651 and € 7684 for scenarios 1-6, respectively. Scenario 2 was the lowest cost option. The extra cost for at least one live birth in scenario 5 was € 629 and in scenario 6 € 630. In these subjects, continuation of treatment for six cycles of clomiphene citrate, 6 or 12 cycles of gonadotrophins and IVF is potentially cost-effective. These results should be confirmed in a randomized clinical trial.

Maternal hormonal interventions as a risk factor for Autism Spectrum Disorder: an epidemiological assessment from India.

Globalization and women empowerment have led to stressful life among Indian women. This stress impairs women's hormonal makeup and menstrual cycle, leading to infertility. National Family Health Survey-3 (NFHS-3) reports a decline in fertility status in India, indicating a rise in various infertility treatments involving hormonal interventions. No studies are available from India on the risk association link between maternal hormonal treatments and ASD. Hence, this study explores the association of maternal hormonal interventions with risk for ASD. Parents of 942 children (471 ASD and 471 controls) across 9 cities in India participated in the questionnaire-based study. The questionnaire was pilot tested and validated for its content and reliability as a psychometric instrument. Data collection was done at 70 centres through direct interaction with parents and with the help of trained staff. Statistical analysis of data was carried out using SAS 9.1.3. Out of the 471 ASD cases analysed, 58 mothers had undergone hormonal interventions (12.3 percent) while there were only 22 mothers among controls who underwent hormonal interventions (4.6 percent). According to logistic regression analysis maternal hormonal intervention (OR=2.24) was a significant risk factor for ASD.