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Reproductive Outcomes After In Vitro Fertilisation Amongst Different Phenotypes of PCOS
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Received: ,
Accepted: ,
How to cite this article: Udhwani RS, Satwik R, Majumdar A, Gupta SM, Tiwari N, Nayar S, et al. Reproductive Outcomes After In Vitro Fertilisation Amongst Different Phenotypes of PCOS. Fertil Sci Res. 2026;13:3. doi: 10.25259/FSR_43_2025
Abstract
Objectives:
To study reproductive outcomes in different polycystic ovary syndrome (PCOS) phenotypes after in vitro fertilisation (IVF) treatments.
Material and Methods:
It is a prospective observational study, conducted from October 2024 to April 2025 at the Centre of IVF and Human Reproduction, Sir Ganga Ram Hospital, New Delhi. Women undergoing IVF were screened for the presence of PCOS and diagnosed based on Rotterdam’s criteria. These women were then subcategorised into the four PCOS phenotypes based on their presenting features. All women with PCOS who were scheduled for assisted reproductive technologies (ART) procedures during the study period and met the inclusion criteria were enrolled in the study. Metabolic disorders were screened with lipid profiles, mean blood glucose levels, and free androgen index. Primary outcomes studied were the β hCG positive rate, implantation rate per transfer, clinical pregnancy rates after the first transfer, and early pregnancy loss rate. Secondary outcomes studied were total dose of gonadotropins used, days of stimulation, number of oocytes retrieved, number of oocytes fertilised, number of cleaved embryos, fertilisation rate, median utilisable blastocyst number per patient, blastulation rate, and utilisable blastocyst rate.
Results:
There were 10 (18.9%) patients with phenotype A, 6 patients in phenotype B (11.3%), 15 in phenotype C (28.3%), and 22 in phenotype D (41.5%). The most prevalent phenotype was D (41.5%). Women with phenotype A though, had higher serum AMH levels (p-value = 0.006), and had a higher median utilisable blastocyst number per patient (p value = 0.024), but the β-hCG positive rate, implantation rates after first embryo transfer, clinical pregnancy rate, and early pregnancy loss rate were similar in the patients with different phenotypes of PCOS. There was no statistical difference in the total dose of gonadotropins used, number of oocytes retrieved, oocytes fertilised, cleaved embryos, fertilisation rate, blastulation rate, and utilisable blastocyst rate. Metabolic disorder screening results indicated higher cholesterol levels in patients with Phenotype B (p value = 0.01), although no difference was noted in levels of HDL, LDL, non-HDL, triglycerides, and mean glucose levels in the patients with different phenotypes of PCOS.
Conclusion:
Our study results suggest that reproductive outcomes, including β hCG positive rate, implantation rate per embryo transfer, clinical pregnancy rate after first embryo transfer, and early pregnancy loss rates, were similar amongst patients with different phenotypes of PCOS. Patients with phenotype A had higher serum AMH levels and had a higher median utilisable blastocyst number per patient, but the utilisable blastocyst rate was comparable across all the phenotypes of PCOS. The study is underpowered to detect differences in reproductive outcomes due to the smaller number of patients enrolled in the study.
Keywords
Clinical pregnancy rate
Implantation rate
PCOS phenotypes
Reproductive outcomes
Utilisable blastocyst rate
INTRODUCTION
Polycystic ovary syndrome (PCOS) is a multifactorial condition characterised by several symptoms and is manifested by metabolic diseases along with impairment of reproductive function.[1] PCOS was diagnosed according to the ESHRE/ASRM Rotterdam criteria (2003), which require the presence of at least two of the following three features: oligo- or anovulation (AO), clinical or biochemical signs of hyperandrogenism, and polycystic ovarian morphology. The overall prevalence of polycystic ovarian pattern has been reported to be in the range of 6%-21%.[2] Infertility in patients with PCOS may be attributed to anovulation occurring in these patients.[3] The Rotterdam criteria identifies four phenotypes in PCOS cases. Phenotype A is characterised by all three features: polycystic ovaries, oligomenorrhea/anovulation, and clinical or biochemical hyperandrogenism (PCO + OA + HA), phenotype B is characterised by hyperandrogenism (clinical or biochemical) and oligomenorrhea/anovulation (HA + OA), phenotype C is characterised by hyperandrogenism (clinical or biochemical) and polycystic ovarian morphology (HA + PCO), and phenotype D is characterised by oligomenorrhea/anovulation and polycystic ovaries (OA + PCO).[4] Approximately two out of every three individuals diagnosed with PCOS have either the A or B phenotype.[5] It has been noted in some studies that different phenotypes of PCOS have different responses to gonadotropins in in vitro fertilization (IVF) cycles[6] that might affect the outcomes of the assisted reproductive technologies (ART) cycles. In most of the studies published in the literature, conflicting results were noted, particularly related to outcomes of ART. An individualised approach to management may be needed in patients with different phenotypes of PCOS to ensure better outcomes.
MATERIAL AND METHODS
A prospective observational study was conducted from October 2024 to April 2025 at the Centre for IVF and Human Reproduction, Sir Ganga Ram Hospital, New Delhi, aiming to study reproductive outcomes in different PCOS phenotypes after IVF treatments. The research/study was approved by the Institutional Review Board at the Indian Fertility Society, Independent Ethical Committee, number F.1/IEC/IFS/2024/No.24, dated 27/12/2024. Women undergoing IVF were screened for PCOS and diagnosed according to the Rotterdam criteria, which require the presence of at least two of the following features:
Oligomenorrhea or anovulation, defined as menstrual cycles longer than 35 days or fewer than 8 cycles per year, or irregular menstrual cycles (cycle length <21 days);
Signs of hyperandrogenism like acne and/or hirsuitism as per the Ferriman-Gallwey scoring system or biochemical hyperandrogenism (free androgen index);
Polycystic ovarian morphology on ultrasound (as per criteria characterised by the presence of ≥20 small follicles, measuring 2-9 mm in at least one ovary and/or ovarian volume >10 cm3, based on transvaginal ultrasonography with a transducer frequency ≥8 MHz).
All patients with PCOS, diagnosed according to the ESHRE/ASRM Rotterdam criteria and undergoing assisted reproductive treatment, with self-eggs between the ages of 23-40 years, were included after written informed consent. Patients with a history of unilateral oophorectomy, uterine conditions like uterine anomalies, fibroids, and adenomyosis, severe endometriosis, and hydrosalpinx were excluded.
All 53 patients included in the study were subcategorised into the four PCOS phenotypes (based on clinical history, examination, and Ferriman-Gallwey scoring), and PCOS panel testing, including lipid profile, mean blood glucose levels, and free androgen index, was done on day 2 of menses.
The transvaginal ultrasound (TVS) of the subjects was done by a single investigator (the most senior) once it was decided that the patient would be enrolled. A baseline hormone profile, including serum folliicle stimulating hormone (FSH), luteinizing Hormone (LH), and AMH, was done using an automated electrochemiluminescent immunoassay system.
Women underwent controlled ovarian stimulation with an antagonist protocol. As per the patient’s age, antral follicle count, BMI, and previous ovarian response, the initial dose of gonadotropin was individualised. Gonadotropin doses were adjusted based on the ovarian response. Oocyte aspiration was performed 35.5 hours post-trigger with a TVS-guided single-lumen oocyte aspiration needle under sedation. Following oocyte retrieval, IVF or intra cytoplasmic sperm injection (ICSI) procedures were carried out. A fertilisation check was undertaken at 17 hours, and resultant embryos were cultured up to the cleavage or blastocyst stage and then frozen. Embryo transfer was done using ultrasound guidance. Luteal phase support was given with vaginal progesterone 400 mg twice daily along with oestradiol valerate 2 mg twice daily in the hormone replacement therapy (HRT) cycle and vaginal progesterone 200 mg twice daily in the natural cycle. Serum beta-human chorionic gonadotropin (β hCG) was measured 14 days after the embryo transfer (ET) procedure. Patients were followed up, and pregnancy outcomes were noted till 12 weeks of pregnancy.
Baseline characteristics, results of metabolic screening, details of ovarian stimulation cycles, their outcomes, details of embryo transfer cycle, and reproductive outcomes were noted.
Primary outcomes studied were β hCG positive rate, implantation rate per transfer, clinical pregnancy rates after first transfer, and early pregnancy loss rate. Secondary outcomes analysed were total dose of gonadotropins used, days of stimulation, number of oocytes retrieved, number of oocytes fertilised, number of cleaved embryos, fertilisation rate, mean utilisable blastocyst number per patient, blastulation rate, and utilisable blastocyst rate.
Definition and Criteria Used
Median utilisable blastocyst number per patient is the median of the number of blastocysts frozen in each patient.
Clinical pregnancy was defined by the occurrence of an intrauterine gestational sac with the presence of cardiac activity.
Early pregnancy loss includes loss of pregnancy up to 12 weeks of gestation, including biochemical pregnancies, blighted ovum, and missed miscarriage.
Data Management and Statistical Analysis
Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS), version 28.0.
Since this study starts with a cohort of PCOS women and not 4 phenotype groups, the sample size estimated by considering the percentage of phenotype C among the PCOS women was 13%, as per the study conducted by Patel et al.[7] With a 95% CI and an error margin of 5%, the sample size was estimated to be 174, but due to time constraints, 53 women were included in the study. This is one of the limitations of the study.
Continuous variables were reported as mean ± standard deviation (SD) for normally distributed data, or as median and interquartile range (IQR) for data not following a normal distribution. • Most variables (e.g., age, weight, Body Mass Index (BMI), high density lipoprotein (HDL), oocyte retrieval (OCR) endometrial thickness, blastulation rate, and fertilisation rate) followed a normal distribution, while several [anti mullerian hormone (AMH), oestradiol, cholesterol, triglycerides, LDL, non-HDL, stimulation dose, oocytes, embryos, Ferriman-Gallwey score, etc.] deviated significantly. This indicates that both parametric and non-parametric tests were appropriately applied depending on the variable distribution.
Categorical variables were presented as frequencies and percentages.
Differences in clinical pregnancy rates among various PCOS phenotypes were assessed using the chi-square test or Fisher’s exact test, as appropriate.
For continuous variables, comparisons across phenotypes, such as total gonadotropin dose, number of oocytes retrieved, and fertilisation rate, were carried out using either one-way analysis of variance (ANOVA) (for normally distributed data) or the Kruskal-Wallis test (for non-normally distributed data).
A p-value of less than 0.05 was considered statistically significant for all analyses.
RESULTS
Baseline Characteristics
In this study, 53 ovarian stimulation cycle data points were collected and analysed. There were 10 (18.9%) patients in phenotype A, 6 (11.3%) in phenotype B, 15 (28.3%) in phenotype C, and 22 (41.5%) in phenotype D. The baseline characteristics were noted in all the phenotypes. It was found that there was no statistical difference in the age distribution, BMI, type of infertility, infertility duration, and history of previous failed embryo transfer cycles, as shown in Table 1; but AMH levels amongst different phenotypes were statistically significantly different. It was noted to be highest in phenotype A with a value of 14 (7.70-18.90) ng/mL compared to 3.99 (3.72-9.00) ng/mL in phenotype B, 4.47 (3.74-6.10) ng/mL in phenotype C, and 5.60 (4.75-7.65) ng/mL in phenotype D (p value = 0.006). It was also noted that there was a difference in the causes for which IVF was undertaken in the different phenotype groups, as depicted in Table 1.
| Variables | Sub-Division | Phenotype A (n = 10) | Phenotype B (n = 6) | Phenotype C (n = 15) | Phenotype D (n = 22) | p value | Effect size (95% CI) |
|---|---|---|---|---|---|---|---|
| Percentage (%) | 18.9 | 11.3 | 28.3 | 41.5 | |||
| Age (years) (Mean ± SD) | 32.30 ± 3.6 | 34.00 ± 4.6 | 33.33 ± 3.6 | 32.5 ± 2.7 | 0.68 | 0.030 (0.0-0.115) | |
| BMI (kg/m2) (Mean ± SD) | 27.5 ± 3.3 | 30.0 ± 7.5 | 26.2 ± 3.9 | 26.9 ± 4.5 | 0.379 | 0.06 (0.0-0.174) | |
| Sr AMH (ng/mL) | 14.00 (7.70-18.90) | 3.99 (3.72-9.00) | 4.47 (3.74-6.10) | 5.60 (4.75-7.65) | 0.006 | 0.19 (0.005-0.472) | |
| Infertility duration | 4.0 (3.0-7.0) | 2.0 (1.5-2.0) | 2.0 (1.0-5.0) | 3.0 (2.0-5.0) | 0.173 | 0.04 (-0.01-0.09) | |
| Type of infertility | Primary | 5 (50.0%) | 5 (83.3%) | 9 (60.0%) | 15 (68.2%) | 0.55 | - |
| Secondary | 5 (50.0%) | 1 (16.7%) | 6 (40.0%) | 7 (31.8%) | |||
| Indication of IVF | Anovulatory PCOS | 5 (50.0%) | 0 (0.0%) | 0 (0.0%) | 5 (22.7%) | 0.037 | - |
| Unexplained | 3 (30.0%) | 2 (33.3%) | 9 (60%) | 9 (40.9%) | |||
| Male factor | 0 (0.0%) | 4 (66.7%) | 5 (33.3%) | 8 (36.4%) | |||
| Others | 2 (20.0%) | 0 (0.0%) | 1 (6.7%) | 0 (0.0%) | |||
| Previous failed ET | 0 | 10 (100.0%) | 5 (83.3%) | 13 (86.7%) | 19 (86.4%) | 0.674 | - |
| 1 | 0 (0.0%) | 1 (16.7%) | 1 (6.7%) | 1 (4.5%) | |||
| 2 | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 2 (9.1%) | |||
| 3 | 0 (0.0%) | 0 (0.0%) | 1 (6.7%) | 0 (0.0%) |
BMI: Body mass index, AMH: Anti mullerian hormone, IVF: In vitro fertilization, ET: Embryo transfer, CI : Confidence interval, SD: Standard deviation, p value significant for type of infertility: 0.55, p value significant for indications of IVF: 0.037.
Metabolic Screening Results
Metabolic screening was done for all patients. There was a statistically significant difference in the cholesterol levels in the different phenotype groups. The levels of cholesterol were higher in phenotype A: 158.0 (148-170) mg/dL and phenotype B: 171 (168-176) mg/dL, while they were 150 (142-160) mg/dL in phenotype C and 156.5 (150-162) mg/dL in phenotype D (p value = 0.01). It was also noted that there was no statistically significant difference in HDL levels, non-HDL levels, low density lipoprotein (LDL) levels, triglyceride levels, mean blood glucose levels, and free androgen index. There was a difference in the Ferriman-Gallwey score amongst different phenotypes, as shown in Table 2.
| Variable | Statistics | Phenotype A (n = 10) | Phenotype B (n = 6) | Phenotype C (n = 15) | Phenotype D (n = 22) | p-value | Effect size (95% CI) |
|---|---|---|---|---|---|---|---|
| Cholesterol | Median (IQR) | 158.0 (148.0-170.0) | 171.0 (168.0-176.0) | 150.0 (142.0-160.0) | 156.5 (150.0-162.0) | 0.01 | 0.16 (0.06-0.26) |
| Triglyceride | Median (IQR) | 125.0 (106.0-136.0) | 121.0 (114.0-132.0) | 122.0 (108.0-128.0) | 124.0 (122.0-160.0) | 0.425 | 0 |
| HDL | Mean ± SD | 54.30 ± 6.86 | 57.17 ± 7.17 | 53.13 ± 5.11 | 51.95 ± 8.98 | 0.482 | 0.049 (0.0-0.154) |
| LDL | Median (IQR) | 90.0 (86.0-98.0) | 97.0 (93.0-101.0) | 88.0 (86.0-92.0) | 93.5 (85.0-98.0) | 0.255 | 0.02 (–0.02-0.06) |
| Non-HDL | Median (IQR) | 116.50 (112.00-120.00) | 118.00 (106.00-130.00) | 124.00 (112.00-130.00) | 120.00 (112.00-132.00) | 0.884 | –0.05 |
| Mean blood glucose | Median (IQR) | 90.00 (86.00-100.00) | 98.00 (95.00-112.00) | 99.00 (88.00-102.00) | 100.00 (88.00-103.00) | 0.767 | –0.04 |
| FAI | Median (IQR) | 6.72 (5.53-6.73) | 3.15 (3.15-3.15) | 3.59 (3.40-3.78) | 3.51 (2.40-3.90) | 0.225 | 0.03 (–0.02-0.007) |
| Ferriman-Gallwey score | Median (IQR) | 15.0 (13.25-16.0) | 15.0 (13.25-16.0) | 16.0 (15.5-20.0) | 4.5 (4.0-5.75) | <0.001 | 0.46 (0.32-0.59) |
HDL: High density lipoprotein, LDL: Low density lipoprotein, FAI: Free androgen index, IQR: Interquartile range. CI: Confidence interval, SD: Standard deviation, Significant p value is <0.05.
Controlled Ovarian Stimulation Cycle Details
Antagonist protocol was used for all the stimulation cycles. It was noted that FSH combined with LH was used more in phenotype A compared to other phenotypes. Though this was mainly due to the clinician’s preference for the addition of LH, it could not be attributed to specific phenotype characteristics. There was no significant difference noted in the total dose of gonadotropins used, subsequent dose change, days of stimulation, trigger, oestradiol levels, and endometrial thickness on the day of trigger, as depicted in Table 3.
| Variable | Sub-Division | Phenotype A (n = 10) | Phenotype B (n = 6) | Phenotype C (n = 15) | Phenotype D (n = 22) | p-value | Effect size (95% CI) |
|---|---|---|---|---|---|---|---|
| Protocol | Antagonist | 10 (100%) | 6 (100%) | 15 (100%) | 22 (100%) | NA | |
| Gonadotropin used | FSH | 6 (60.0%) | 6 (100%) | 14 (93.3%) | 21 (95.5%) | 0.041 | - |
| 4 (40.0%) | 0 (0.0%) | 1 (6.7%) | 1 (4.5%) | ||||
| Total dose (Median (IQR)) | 1800 (1325-2325) | 1763 (1350-2250) | 1575 (1350-1775) | 1375 (1250-1875) | 0.536 | –0.02 | |
| Subsequent dose change | No | 3 (30.0%) | 1 (16.7%) | 7 (46.7%) | 9 (40.9%) | 0.529 | |
| 2 (20.0%) | 0 (0.0%) | 0 (0.0%) | 2 (9.1%) | ||||
| 5 (50.0%) | 5 (83.3%) | 8 (53.3%) | 11 (50.0%) | ||||
| Days of stimulation | 8.5 (8.0-13.0) | 8.0 (7.0-11.0) | 8.0 (7.0-9.0) | 8.0 (8.0-9.0) | 0.225 | 0.03 (–0.02-0.008) | |
| Trigger | Decapeptyl | 10 (100.0%) | 3 (50.0%) | 10 (66.7%) | 19 (86.4%) | 0.087 | |
| 0 (0.0%) | 2 (33.3%) | 3 (20.0%) | 3 (13.6%) | ||||
| 0 (0.0%) | 1 (16.7%) | 2 (13.3%) | 0 (0.0%) | ||||
| Terminal Oestradiol | 2670.5 (1961.0-4381.0) | 2303.5 (1725.0-2839.0) | 2576.0 (1872.0-4720.0) | 2682.0 (1482.0-3826.0) | 0.795 | –0.04 | |
| OCR endometrial thickness | 8.0 (7.5-8.8) | 9.2 (7.4-11.4) | 7.7 (7.5-9.7) | 8.5 (7.79.5) | 0.331 | 0.01 (–0.02-0.03) | |
FSH: Follicle stimulating hormone, LH: Luteinizing hormone, IQR: Interquartile range, OCR: Oocyte retrieval. CI: Confidence interval, NA: Not applicable, Significant p-value is < 0.05.
Controlled Ovarian Stimulation Cycle Outcomes
Median utilisable blastocyst number per patient was highest in patients with phenotype A: 6 (8-4) compared to phenotype B: 2 (3-1), phenotype C: 2 (4-1), and phenotype D: 4 (7-2) (p value = 0.024). While the total number of oocytes retrieved, oocytes fertilised, number of cleaved embryos, fertilisation rate, blastulation rate, and utilisable blastocyst rate were similar amongst the patients in different phenotypes as depicted in Table 4.
| Variable | PhenotypeA (n = 10) | Phenotype B (n = 6) | Phenotype C (n = 15) | Phenotype D (n = 22) | p-value | Effect size (95% CI) |
|---|---|---|---|---|---|---|
| Number of oocytes | 23 (27-20) | 16 (2414) | 18 (24-10) | 19 (23-15) | 0.264 | 0.02 (–0.02-0.06) |
| Number of oocytes fertilised | 14 (219) | 9 (14-5) | 9 (13-7) | 12 (13-9) | 0.169 | 0.04 (–0.01-0.09) |
| Number of cleaved embryos | 13 (21-9) | 9 (13-5) | 9 (13-7) | 13 (15-9) | 0.187 | 0.03 (–0.02-0.08) |
| Fertilisation rate | 70.71 (87.50-44.44) | 46.53 (70.8335.71) | 58.33 (86.67-41.38) | 58.57 (70.37-42.86) | 0.499 | -0.01 |
| Median utilisable blastocyst number per patient | 6 (8-4) | 2 (3-1) | 2 (4-1) | 4 (7-2) | 0.024 | 0.12 (0.03-0.21) |
| Median blastulation rate | 62.4 (75.0-46.3) | 34.3 (40.0-20.0) | 35.7 (66.7-14.3) | 58.2 (75.00-33.3) | 0.268 | 0.02 (–0.02-0.05) |
| Utilisable blastocyst rate | 50.05 (55.60-22.20) | 26.65 (40.00-17.60) | 28.60 (55.60-14.30) | 42.00 (66.70-16.70) | 0.531 | –0.02 |
CI: Confidence interval, Significant p-value is <0.05.
Embryo Transfer Cycle Details
Out of the 53 ovarian stimulation cycles, 52 patients underwent embryo transfer, as one patient did not form a blastocyst in the initial stimulation cycle. There was a difference in the preparation protocol used for embryo transfer amongst women with different phenotypes of PCOS, as women with phenotype C had ovulatory cycles, so a natural cycle protocol was used for endometrial preparation for embryo transfer in some patients. There was no difference in the endometrial thickness, number of embryos transferred, stage of embryo, and grade of embryo transferred in patients with different phenotypes as depicted in Table 5.
| Variable | Sub-Division | Phenotype A (n = 10) | Phenotype B (n = 6) | Phenotype C (n = 15) | Phenotype D (n = 21) | p-value | Effect size (95% CI) |
|---|---|---|---|---|---|---|---|
| Preparation method | Natural cycle + modified natural cycle | 3 (30.0%) | 3 (30.0%) | 9 (60.0%) | 18 (85.7%) | 0.015 | - |
| HRT | 7 (70.0%) | 3 (50.0%) | 6 (40.0%) | 3 (14.3%) | |||
| Endometrial thickness | 8.0 (7.5-8.8) | 9.2 (7.4-11.4) | 7.7 (7.5-9.7) | 8.5 (7.79.5) | 0.703 | –0.03 | |
| Embryo stage | Day 3 | 0 (0%) | 1 (16.7%) | 1 (6.7%) | 0 (0%) | 0.451 | |
| Day 5 | 8 (80.0%) | 5 (83.3%) | 10 (66.7%) | 17 (81.0%) | |||
| Day 6 | 2 (20.0%) | 0 (0%) | 4 (26.7%) | 4 (26.7%) | |||
| Number transferred | 1.00 (1.0-1.0) | 1.00 (1.0-1.0) | 1.00 (1.0-1.0) | 1.00 (1.0-1.0) | 0.584 | –0.02 | |
| Embryo grade | Good | 10 (100.0%) | 6 (100.0%) | 13 (86.7%) | 20 (95.2%) | 0.487 | |
| Average | 0 (0%) | 0 (0%) | 2 (13.3%) | 0 (0%) | |||
| Poor | 0 (0%) | 0 (0%) | 0 (0%) | 1 (4.8%) |
HRT: Hormone replacement therapy. CI: Confidence interval, Significant p-value is <0.05.
Outcomes of the Embryo Transfer Cycle
The β hCG positive rate (p value = 0.362), implantation rate per embryo transfer (p value = 0.977), and clinical pregnancy rates after the first embryo transfer (p value = 0.935) were similar amongst women with different phenotypes of PCOS. There was no difference in the early pregnancy loss rate amongst women in different phenotypes as well (p value = 0.956) as depicted in Table 6.
| Outcome | Phenotype A (n = 10) | Phenotype B (n = 6) | Phenotype C (n = 15) | Phenotype D (n = 21) | p-value |
|---|---|---|---|---|---|
| β-hCG positive | 6/10 (60.0%) | 6/6 (100.0%) | 9/15 (60.0%) | 14/21 (66.7%) | 0.362 |
| Implantation rate per transfer | 6/10 (60.0%) | 4/6 (66.7%) | 8/15 (53.3%) | 12/21 (57.1%) | 0.977 |
| Clinical pregnancy rate | 6/10 (60.0%) | 4/6 (66.7%) | 8/15 (53.3%) | 11/21 (52.4%) | 0.935 |
| Early pregnancy loss rate | 1/6 (16.7%) | 2/6 (33.3%) | 3/9 (33.3%) | 4/14 (28.6%) | 0.956 |
hCG: Human chorionic gonadotropin. , Significant p-value is <0.05.
DISCUSSION
The study was undertaken to determine if there was any difference in the reproductive outcomes and metabolic disorders amongst women with different phenotypes of PCOS. It was noted that the prevalence of phenotype D was the highest, which was consistent with studies undertaken by Wang et al.[8] and Nayar et al.[9]
In our study, the second most prevalent phenotype was type C, followed by phenotype A and B. When baseline characteristics were analysed, it was found that phenotype A had the highest levels of serum AMH, similar to the results in the study by Patel et al.[7] and Nayar et al.[9]
We observed that there was a difference in the indication for IVF in patients with different phenotypes, but the other baseline characteristics were similar in the patients in different phenotype groups.
Metabolic screening results showed the highest levels of cholesterol in women with phenotype B compared to other phenotypes. While the levels of HDL, LDL, non-HDL, and triglyceride were similar in the patients with different phenotypes, there was no difference in the mean glucose levels, as well as the free androgen index, in the patients with different phenotypes of PCOS. There was a difference in the Ferriman-Gallwey score, as phenotype D was expected to have a lower score, as less or no androgenic features occur in phenotype D. In a study done by Eftekhar et al.,[10] a difference was noted in the fasting blood glucose levels in patients with different phenotypes of PCOS, but currently there is limited literature on the levels of blood sugar in patients with different phenotypes of PCOS.
The analysis of the stimulation cycle used in women with different phenotypes of PCOS suggests that there was no significant difference in the number of days required for the stimulation cycle. In a study undertaken by Patel et al.,[7] similar findings were noted, but the difference was not statistically significant. Also, in the current study, we found no difference in total dose of gonadotropin, subsequent dose change, trigger used, endometrial thickness on the day of trigger, and oestradiol levels on the day of the trigger. Although in a study done by Patel et al.,[7] the authors noted the need for a higher dose of gonadotropin for the stimulation cycle of patients with phenotype A, and in a study by Nayar et al.,[9] the authors noted the need for a higher dose of gonadotropin by women with phenotype B, the study by Wang et al.[8] showed findings similar to our study. They reported no difference in the total dose of gonadotropins used and more number of days of stimulation for women with phenotype A.
In our study, it was noted that although there was a difference in the levels of serum AMH, there was no statistically significant difference in the number of oocytes retrieved, oocytes fertilised, cleaved embryos, and fertilisation rate. Eftekhar et al.,[10] also found no difference in the number of oocytes retrieved despite higher serum AMH levels in women with phenotype A. A higher median number of utilisable blastocysts per patient was noted in women with phenotype A, but the blastulation rate and utilisable blastocyst rate were similar in patients with different phenotypes of PCOS.
When the embryo transfer cycle details were analysed, it was seen that there was a difference in the method used for endometrial preparation for embryo transfer, as few patients with phenotype C were planned with the natural cycle method, as the cycles were ovulatory. Also, the method used was determined by a number of other factors, like the clinician’s preference, as well as patient factors like ability to follow up and response to ovulation induction drugs if used previously. Endometrial thickness, number of embryos transferred, stage of embryo transferred, and grade of embryo transferred were comparable in the patients with different phenotypes.
The reproductive outcomes of the patients in different phenotypes were similar when the β-hCG positive rate, clinical pregnancy rate after first embryo transfer, early pregnancy loss, and implantation rates per embryo transfer were compared. The study by Nayar et al.[9] found a higher statistically significant clinical pregnancy rate in patients with phenotype D, and Patel et al.,[7] reported a higher clinical pregnancy rate in patients with phenotype D, though it was not statistically significant. Eftekhar et al.,[10] reported no difference in the clinical pregnancy rate and implantation rates, similar to our study. Also, studies by Selcuk et al.[11] and Wang et al.[8] also found no difference in the clinical pregnancy and live births amongst women with different phenotypes of PCOS.
Strengths
Prospective observational study with meticulously collected data.
Metabolic disorder screening was done with lipid profile, mean blood glucose levels, and free androgen index, which have been studied in a few studies only.
Limitations
This was a single-centre study with a relatively small sample size and a shorter study duration. As a result of the limited timeframe, patients were only followed up after their first embryo transfer.
CONCLUSION
This prospective cohort study suggests that women with phenotype A had higher serum AMH levels and median utilisable blastocyst number per patient, but utilisable blastocyst rate was comparable across all the phenotypes of PCOS. Study results suggest that reproductive outcomes, including β hCG positive rate, implantation rate per embryo transfer, clinical pregnancy rate after first embryo transfer, and early pregnancy loss rates, were similar amongst patients with different phenotypes of PCOS. Future studies with a large sample size are recommended to enhance the accuracy and reliability of the results. Our study is underpowered to detect differences in reproductive outcomes due to the less number of patients enrolled in the study.
Author Contributions:
RSU: Conceptualisation, Study design, Defination of intellectual content, Data acquisition, Data analysis, Statistical analysis., literature research; RS: Conceptualisation, Study design, Definition of intellectual content, Data acquisition, Data analysis, Statistical analysis; AM: Conceptualisation, Study design, Literature search, Data acquisition; SMG: Conceptualisation, Definition of intellectual content, Data acquisition; NT: Conceptualisation, Study design, Definition of intellectual content, Data acquisition; SN: Study design, Data acquisition; BS: Study design, Data acquisition.
Ethical approval:
The research/study approved by the Institutional Review Board at Indian Fertility Society, Independent Ethical Committee, approval number F.1/IEC/IFS/2024/No.24, dated 27th December 2024.
Declaration of patient consent:
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Conflicts of interest:
There are no conflicts of interest.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation:
The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.
Financial support and sponsorship: Nil.
References
- Criteria, Prevalence, and phenotypes of polycystic ovary syndrome. Fertil Steril. 2016;106:6-15.
- [CrossRef] [PubMed] [Google Scholar]
- Ovarian volume and PCOS: A controversial issue. Gynecol Endocrinol. 2018;34:229-32.
- [CrossRef] [PubMed] [Google Scholar]
- Assessment of cardiovascular risk and prevention of cardiovascular disease in women with the polycystic ovary syndrome: A consensus statement by the androgen excess and polycystic ovary syndrome (AE-PCOS) society. J Clin Endocrinol Metab. 2010;95:2038-49.
- [CrossRef] [PubMed] [Google Scholar]
- Ovarian response to controlled ovarian stimulation in women with different polycystic ovary syndrome phenotypes. Gynecol Endocrinol. 2018;34:518-23.
- [CrossRef] [PubMed] [Google Scholar]
- Comparing assisted reproductive outcomes in women with different polycystic ovary syndrome phenotypes undergoing freezed embryo transfer. J Hum Rep Sci. 2023;16:340-5.
- [CrossRef] [PubMed] [Google Scholar]
- Association of polycystic ovary syndrome phenotypes with adverse pregnancy outcomes after in-vitro fertilization/intracytoplasmic sperm injection. Front Endocrinol. 2022;13:889029.
- [CrossRef] [PubMed] [Google Scholar]
- Does controlled ovarian hyperstimulation response varies with PCOS phenotypes: A prospective cohort study at a tertiary infertility centre in INDIA. Fertil Steril. 2020;114:e403.
- [CrossRef] [Google Scholar]
- Assisted reproductive outcomes in women with different polycystic ovary syndrome phenotypes. Int J Gynecol Obstetr. 2019;144:147-52.
- [CrossRef] [PubMed] [Google Scholar]
- Characteristics and outcomes of in vitro fertilization in different phenotypes of polycystic ovary syndrome. Turk J Obstet Gynecol. 2016;13:1-6.
- [CrossRef] [PubMed] [Google Scholar]