Updates from

ESHRE 2024
Polycystic Ovary
Syndrome: Understanding
Hormonal Dysregulation and
Treatment Strategies
Topic Name Slide No.
Association between advanced maternal age in women with polycystic ovary syndrome and adverse obstetric outcomes 3-4

Anxiety, depression, and body image among infertile women with and without polycystic ovary syndrome 5-6

The ULTRA trials: transvaginal ultrasound-guided ovarian ablation in women with PCOS-related infertility: clinical and 7-8
endocrine outcomes of first–in-human feasibility trial

Should the ovarian ultrasound markers for the diagnosis of PCOS be revised? 9-11

Underlying Molecular Mechanisms of Polycystic Ovary Syndrome and Morphology: Focusing on the Ovary 12-13

Identification of novel biomarkers for the detection of polycystic ovary syndrome (PCOS) in adolescents and adult 14-15
women
The impact of polycystic ovary syndrome (PCOS) on placental pathology among singleton livebirths conceived following 16-17
in-vitro fertilization (IVF) or ovulation induction/intrauterine insemination (OI/IUI) treatments
Effect of body mass index on early and late pregnancy loss in women with polycystic ovary syndrome undergoing in vitro 18-19
fertilization and embryo transfer
Distinctive proteomic profiling and phenotypic correlations of plasma extracellular vesicles provided clues for their 20-21
regulatory roles in the pathogenesis of polycystic ovarian syndrome
Impact of low versus air oxygen tension on the oocyte maturation in PCOS women undergoing capacitation IVM:A 22-23
sibling oocyte pilot study
Association between advanced maternal age in women with polycystic ovary syndrome and
adverse obstetric outcomes

Background
 Polycystic Ovary Syndrome (PCOS): PCOS is known to be a risk factor for adverse obstetric outcomes.
 Advanced Maternal Age (AMA): AMA is also recognized as an independent risk factor for complications during pregnancy.
 Research Gap: The role of AMA on pregnancy complications in women with PCOS has not been investigated.

Objective
 To determine the independent effect of AMA on the likelihood of experiencing adverse pregnancy, delivery, and neonatal outcomes in pregnant
women with PCOS.

Methods
 Study Design: A retrospective population-based study performed using data from the Healthcare Cost and Utilization Project Nationwide Inpatient
Sample (HCUP-NIS) database.
 Study Period: 2004 and 2014.
 Population: The study analyzed 14,846 women diagnosed with PCOS, of which 943 (6.35%) were of significant advanced maternal age (38-43
years).
Association between advanced maternal age in women with polycystic ovary syndrome and
adverse obstetric outcomes

Results Pregnancy and Delivery Outcomes Adjusted OR (95%CI) Adjusted p-value

Pregnancy induced hypertension 1.32 (1.09-1.59) P=0.004
Gestational hypertension 1.21 (0.91-1.62) P=0.19
 Women with PCOS and AMA were more likely to develop Preeclampsia 1.51 (1.16-1.98) P=0.003
Eclampsia NA P=0.99
pregnancy-induced hypertension (adjusted OR 1.32, 95% CI 1.09- Superimposed preeclampsia/ eclampsia 1.05 (0.71-1.55) P=0.81
1.59), preeclampsia, gestational diabetes mellitus, and had an Gestational diabetes 1.66(1.40-1.97) P=<0.001
increased risk of cesarean section, after controlling for Placenta previa 1.63 (0.77-3.43) P=0.20
PPROM 0.88 (0.51-1.54) P=0.66
confounding demographics. (Table 1) Preterm delivery 0.99(0.79-1.25) P=0.97
 Neonatal Outcomes: There was no difference in the rate of small Abruptio plecenta 1.48 (0.89-2.49) P=0.13
Chorioamnionitis 1.26(0.83-1.92) P=0.28
for gestational age (SGA) infants, intrauterine fetal demise (IUFD), Operative vaginal delivery 0.94 (0.62-1.44) P=0.78
or infants with congenital anomalies between the two groups. Caesarean delivery 1.20(1.10-1.43) P=0.036
Spontaneous vaginal delivery 0.84 (0.71-0.99) P=0.049
Hysterectomy 3.19 (0.58-17.50) P=0.18
Postpartum hemorrhage 1.069(0.72-1.57) P=0.77
Wound complications 1.63 (0.85-3.12) P=0.14
Maternal death NA P=0.975
Transfusion 0.91 (0.47-1.76) P=0.78

Table 1 – Pregnancy and Delivery Outcomes

Conclusion
 The study demonstrates that AMA in women with PCOS significantly increases the risk of adverse obstetric outcomes. These findings underscore the
importance of integrating the consideration of AMA into the management and care planning for pregnant women with PCOS, ensuring they receive
tailored perinatal care to mitigate these risks.
Anxiety, depression, and body image among infertile women with and without polycystic
ovary syndrome

Background
 PCOS is linked to increased anxiety, depression, and body image issues.
 Guidelines recommend routine mental health screening for women with PCOS.
 Previous studies compared PCOS women to healthy women without fertility problems.

Objective
 To determine the prevalence of symptoms associated with anxiety, depression, and body appreciation, among infertile women with and without
PCOS.

Methods
 Study population: 1,025 women undergoing infertility treatment (502 with PCOS, 523 with other diagnoses).
 Data collection: Online questionnaires (HADS, BAS-2).
 Primary outcomes: Clinically relevant symptoms of anxiety, depression, and Mean BAS-2 scores.
 Secondary outcomes: Anxiety, depression scores, and dichotomous/continuous outcomes.
Anxiety, depression, and body image among infertile women with and without polycystic
ovary syndrome

Results
Adjusted OR PCOS No PCOS
Anxiety
 Anxiety: 33.1% of women with PCOS vs. 31.0% with other diagnoses Score ≥ 11 33% 31%

(adjusted OR: 0.99, 95% CI 0.74–1.31) (Figure 1).

 Depression: 15.5% of women with PCOS vs. 14.5% with other diagnoses Score ≥ 8 57% 54%

(adjusted OR: 1.04, 95% CI 0.71–1.50) (Figure 1). Depression

 Body Appreciation: Women with PCOS reported slightly lower body Score ≥ 11
16% 15%

appreciation (adjusted mean difference: -1.34, 95% CI -2.32 to -0.36).

Score ≥ 8 34% 32%

.25 .5 1 2 4
More in other diagnoses More in PCOS

*Adjusted for age, BMI, and duration of infertility

Conclusion
 The study demonstrates that women with PCOS reported lower body satisfaction, but no increased symptoms of anxiety or depression. Addressing
mental health concerns in women experiencing infertility can enhance their self-esteem and overall well-being.
The ULTRA trials: Transvaginal ultrasound-guided ovarian ablation in women with PCOS-
related infertility: Clinical and endocrine outcomes of first–in-human feasibility trial

Background
 Laparoscopic ovarian drilling (LOD) is effective for PCOS-related infertility but is invasive and requires general anesthesia.
 No standardization of LOD technique among surgeons.
 TVUS-guided ovarian ablation as a second line ovulation induction in PCOS women
 May Health System offers a less invasive, office-based ovarian ablation without general anesthesia, similar to oocyte retrieval.

Objective
 Evaluate clinical and endocrine outcomes at six-month follow-up after ovarian ablation.

Methods
 Participants: Clomiphene-/letrozole (CC/LTZ) resistant PCOS women diagnosed by modified Rotterdam criteria.
 Procedure: TVUS-guided ovarian ablation using May Health system.
 Follow-up: Weekly serum progesterone for 12 weeks, clinical evaluations at 3 and 6 months, and follow-up calls at 9, 12, and 24 months (EU sites
only).
 Outcomes: Serum hormone levels (AMH, testosterone, FAI, LH) and ovarian volume compared at baseline, 3, and 6 months.
The ULTRA trials: Transvaginal ultrasound-guided ovarian ablation in women with PCOS-
related infertility: Clinical and endocrine outcomes of first–in-human feasibility trial

Results

 31 participants underwent the procedure; 23 completed a six-month follow-up.

 Spontaneous ovulation rate: 44% (14/31) at 3 months, increasing to 65% (20/31) by 9 months after restarting CC/LTZ (Figure 1).
 Pregnancy outcomes: 10 participants (32%) conceived: 7 live births, 2 ongoing pregnancies, 1 miscarriage.
 There was a significant decrease in median serum AMH from baseline to 3 and 6 months post-procedure (Figure 2).

250

100% 200
**p<0.01

Serum AMH pmol/L

80% 65% 150

60% 44% 100

40%
32%
50
20%

0% 0
Baseline 3 Month 6 Month
Ovulation at 3-M Ovulation at 9-M Pregnancy to date
Figure 1. Clinical outcomes of TVUS-Ovarian ablation Figure 2. Serum AMH at baseline, 3- 8. 6-months FU after
ovarian ablation
The ULTRA trials: Transvaginal ultrasound-guided ovarian ablation in women with PCOS-
related infertility: Clinical and endocrine outcomes of first–in-human feasibility trial

Results
20
(p=0.047)

Magnitude (%) AMH change at 3M

0
 Greater AMH decline in ovulators (responders (-23.7%) vs.
non-responders (-7.3%, p=0.047)) was observed, leading to
-20
subsequent resumption of ovulation.
 There was a significant decrease in ovarian volume from
baseline to 6 months (13.42 ml to 9.56 ml) (Figure 3). -40

 No significant changes in mean testosterone, LH, or FAI at 3 or

6 months. -60

-80

Nonresponders Responders

Figure 2. Magnitude of AMH decline in responders

versus non-responders

Conclusion
 May Health System may be an effective, office-based treatment for PCOS. AMH decline suggests a potential mechanism for ovarian rebalancing.
Should the ovarian ultrasound markers for the diagnosis of PCOS be revised?

Background
 Polycystic Ovary Syndrome (PCOS) is defined by three key characteristics: irregular or absent ovulation, elevated levels of androgens (male
hormones), and the presence of multiple cysts on the ovaries, known as polycystic ovary morphology (PCOM).
 In the 2018 International PCOS Guideline, the threshold for antral follicle count to define polycystic ovary morphology (PCOM) was raised from 12 to
20, reflecting the enhanced accuracy of modern ultrasound devices.
 The threshold of ≥ 10 mL for ovarian volume (OV) was kept unchanged. However, there is ongoing debate regarding these cut-off values, as many
studies have been based on relatively small sample sizes.

Objective
 To evaluate and compare OV and Follicle number per ovary (FNPO) in a large well-phenotyped cohort of women with PCOS and in controls.

Methods
 Data from an endocrine screening study was utilized, involving women diagnosed with PCOS based on the Rotterdam criteria, as well as a control
group of women.
 The control group consisted of women who had regular menstrual cycles, normal hormone levels, and no diagnosis of PCOS.
 The data encompassed both low-frequency (< 8 MHz) and high-frequency (> 8 MHz) ultrasound probes.
 Various PCOS phenotypes were evaluated using the different PCOM criteria.
Should the ovarian ultrasound markers for the diagnosis of PCOS be revised?

Results
 Medians of FNPO were above the cut-off value (12 or 20) in all age groups, except for the group ≥ 40 years.
 Optimal cut-off (20-34.9 years):-Left FNPO 22 -Left OV 6.5 mL -Right FNPO 19.5 -Right OV 7.4 mL
 Optimal cut-off (35-39.9 years):-Left FNPO 14.5 -Left OV 8.0 mL-Right FNPO 14.0 -Right OV 7.2 mL

Controls
80 80 Controls Cases 30
Controls
Controls
Cases Cases 30 Cases

60 60
Right FNPO 20 20
Left FNPO

Right OV
Left OV
40 40

10 10
20 20

0 0 0 0
15-19.9 20-24.9 25-29.9 30-34.9 35-39.9 ≥40 15-19.9 20-24.9 25-29.9 30-34.9 35-39.9 15-19.9 20-24.9 25-29.9 30-34.9 35-39.9 15-19.9 20-24.9 25-29.9 30-34.9 35-39.9
Age groups Age groups Age groups Age groups

Figure 1. Boxplots of FNPO and OV in cases and controls

Conclusion
 FNPO appears to be a more reliable marker for polycystic ovary morphology (PCOM) than ovarian volume (OV). The cut-off value for diagnosing PCOM
based on ovarian volume (OV) should be reconsidered or potentially eliminated. Relying solely on FNPO as a diagnostic marker for PCOM does not
appear to lead to underdiagnosis.
Underlying Molecular Mechanisms of Polycystic Ovary Syndrome and Morphology: Focusing
on the Ovary

Background
 Polycystic Ovary Syndrome (PCOS) is a major cause of female infertility, marked by abnormal follicular development, hormonal imbalances, and
reproductive symptoms like anovulation, poor oocyte quality, and hyperandrogenism.
 Polycystic Ovarian Morphology (PCOM) is found in 16-25% of women with regular menses, but its clinical significance and relationship with PCOS
remain uncertain.

Objective
 To identify the molecular mechanisms behind ovarian alterations in PCOS using high-throughput techniques to improve clinical management and
differentiate it from PCOM.

Methods
 Cross sectional molecular study including patients undergoing an IVF cycle between 2019-2022.
 Women meeting two or more Rotterdam criteria were classified as having PCOS, while PCOM was defined by polycystic ovarian morphology on
ultrasound with regular ovulatory cycles.
 Fertile control patients were also used as a reference group.
 Granulosa cells (GCs) and follicular fluid (FF) samples were collected during oocyte retrieval for RNA-Seq and proteomic analysis, respectively.
Underlying Molecular Mechanisms of Polycystic Ovary Syndrome and Morphology: Focusing
on the Ovary

Results

 GCs RNA-seq data showed clear distinctions between PCOS and control women, with 526 differentially expressed genes (DEGs), and oxidative
phosphorylation was the most enriched pathway.
 Thirty-four DEGs were identified between PCOS and PCOM GCs, with oxidative phosphorylation as the main enriched process.
 Six of the 12 shared DEGs were upregulated mitochondrial genes in PCOS compared to PCOM and controls.
 These findings suggest that PCOS GCs are associated with dysregulation in oxidative phosphorylation, possibly linked to changes in mitochondrial
electron transport chain genes.
 Proteomic analysis identified 37 differentially expressed proteins (DEPs) in the FF of PCOS compared to controls, primarily involved in the
complement and coagulation cascades, PI3K-AKT pathway, oocyte meiosis, and ferroptosis.

Conclusion
 Dysregulations in oxidative phosphorylation and the complement system may play a crucial role in the multifactorial nature of PCOS, affecting
folliculogenesis and oocyte quality. Studying these mechanisms can provide new insights into potential biomarkers for more accurate diagnosis and
management of PCOS.
Identification of novel biomarkers for the detection of polycystic ovary syndrome (PCOS) in adolescents and adult women

Background
 International evidence-based guidelines recommend using the Rotterdam criteria for diagnosing PCOS.
 Timely diagnosis of PCOS, along with appropriate monitoring, follow-up, and early intervention, can help reduce the risk of associated
comorbidities.
 There is a need for biomarkers to facilitate earlier diagnosis of PCOS in adolescents and women of reproductive age.

Objective
 To identify the novel biomarkers to distinguish between PCOS-positive cases and healthy PCOS-negative controls in women as early as
adolescence

Methods
 This retrospective study utilized banked serum samples from women with PCOS (confirmed using the Rotterdam criteria) and healthy controls
from previous studies.
 Cohort 1: n=90 cases (phenotype A, n=30; B, n=20; C, n=20; D, n=20); n=47 controls. Cohort 2: n=240 cases (15–19 years, n=70; 20–24 years, n=99;
25–40 years, n=71); n=48 controls; median 26.0 years.
Identification of novel biomarkers for the detection of polycystic ovary syndrome (PCOS) in adolescents and adult women

Results
 All biomarkers and biomarker ratios effectively
distinguished PCOS cases from controls, Biomarker A B C D
regardless of PCOS phenotype and age group. METRNL 0.90 0.93
 Serum 0.99 0.95
METRNL concentrations were (pg/mL) (0.78-1.00) (0.84-1.00) (0.97-1.00) (0.86-1.00)
numerically lower, while serum FGFBP1 and
FGFBP1 0.88 0.88 0.88 0.84
LTA4H concentrations were numerically higher
(pg/mL) (0.79-0.96) (0.79-0.96) (0.80-0.96) (0.74-0.94)
in PCOS cases compared to controls.
 The corresponding AUCs confirmed that LTA4H 0.90 0.88 0.76 0.85
individual biomarkers and biomarker ratios (ng/mL) (0.82-0.98) (0.78-0.97) (0.64-0.88) (0.75-0.95)
effectively distinguished PCOS cases from FGFBP1: 0.95 0.99 1.00 0.99
controls, regardless of PCOS phenotype and METRNL (0.87-1.00) (0.97-1.00) (0.99-1.00) (0.98-1.00)
across various age categories. LTA4H 0.99 0.99 0.97 0.97
METRNL (0.97-1.00) (0.97-1.00) (0.93-1.00) (0.93-1.00)
Figure 1. AUC values across PCOS phenotypes (A–D)

Conclusion
 Circulating meteorin-like protein (METRNL), fibroblast growth factor binding protein-1 (FGFBP1) and leukotriene A4 hydrolase (LTA4H) identified PCOS as
early as adolescence, independent of PCOS phenotype.
The impact of polycystic ovary syndrome (PCOS) on placental pathology among singleton livebirths conceived following
in-vitro fertilization (IVF) or ovulation induction/intrauterine insemination (OI/IUI) treatments

Background
 Women with PCOS have a higher risk of placental-mediated maternal and neonatal adverse outcomes.
 However, the impact of PCOS on placental pathology in singleton live births conceived through treatments remains unclear.

Objective
 To evaluate any associations between PCOS and placental pathology in singleton live births conceived through ovarian induction/intrauterine
insemination (OI/IUI) or in vitro fertilization (IVF).

Methods
 A retrospective review was conducted on 1,398 singletons with available placental pathology data from an academic fertility center.
 PCOS patients (n: 193) were compared to non-PCOS (n: 1196).
 Outcomes: Placental pathology classified as anatomic, inflammatory, infectious, and vascular.
The impact of polycystic ovary syndrome (PCOS) on placental pathology among singleton livebirths conceived
following in-vitro fertilization (IVF) or ovulation induction/intrauterine insemination (OI/IUI) treatments

Results
 PCOS vs. non-PCOS patients were in average
Figure 1 Vascular
younger (32.9 vs. 35.1 years, p<0.001), with 1.3
higher mean BMI (26.1 vs. 24.8 kg/m2, p 0.003).
1.2
 In both the total population and when
adjOR
separated by IVF versus OI/IUI conceptions and 1.1
- 95%CI
fresh versus frozen (FET) transfers, adjusted
1
odds ratios (adjOR) showed no differences Non-PCOS: ref.
between the groups in terms of anatomical, 0.9

inflammatory, or infectious abnormalities.

 Vascular abnormalities were similar between 0.8

groups in the total population, as well as in 0.7

fresh and frozen (FET) cycles. However, lower ALL PATIENTS OI/IUI Fresh IVF FET
odds of vascular abnormalities were observed
among PCOS patients in OI/IUI treatments. Figure 1. Vascular abnormalities

Conclusion
 No association was observed between PCOS and placental pathology in singleton live births conceived with fertility treatments. However, isolated
findings suggest potential links and warrant further investigation.
Effect of body mass index on early and late pregnancy loss in women with polycystic ovary
syndrome undergoing in vitro fertilization and embryo transfer

Background
 A high BMI in women with PCOS is clearly associated with pregnancy loss. However, data are limited for differentiating between early and late
pregnancy loss in PCOS women across different BMI levels and ages.

Objective
 To evaluate whether early and late pregnancy loss both affected by elevated body mass index (BMI) in women with polycystic ovary syndrome
(PCOS) undergoing IVF-ET

Methods
 A retrospective cohort study of PCOS women with a positive human chorionic gonadotropin (hCG) following IVF-ET treatment at a university
hospital reproductive center from January 2015 to October 2022 was conducted.
 The study investigated early pregnancy loss (≤12 weeks, including biochemical pregnancy loss) and late pregnancy loss (>12 weeks) in an
overweight group (BMI ≥24 kg/m²) compared to a normal BMI group (BMI <24 kg/m²).
Effect of body mass index on early and late pregnancy loss in women with polycystic ovary
syndrome undergoing in vitro fertilization and embryo transfer

Results
 Out of 3,213 women with PCOS who conceived through IVF-ET treatment, 1,715 (53.4%) were categorized as overweight, while 1,498 (46.6%) were
in the normal weight group.
 Overweight women with PCOS had higher serum levels of basal total testosterone and androstenedione. Early pregnancy loss (EPL) occurred in
24.2% (415) of overweight women, compared to 21.6% (323) of those with normal weight.
 Overweight women experienced higher rates of late pregnancy loss (LPL), with 6.6% in the overweight group compared to 3.3% in the normal weight
group.
 In subgroup analyses, young and advanced-age women with PCOS both had increased chances of LPL with elevated BMI.
Fertility outcomes after IVF-ET stratified by female ages
Logistic regression analysis of factors related to late PL
Overweight Normal P
OR(95%CI) Wals p OR(95%CI)
N=1715 N=1498
Pregnancy loss 529 (30.8) 372 (24.8) 1.35 (1.16, 1.58) <0.001 BMI 6.367 0.012 1.08 (1.02, 1.15)
Early PL 415 (24.2) 323 (21.6) 1.16 (0.98, 1.37) 0.077 0.99 (0.92, 1.06)
Age 0.128 0.720
<35 years 315 (22.5) 239 (19.3) 1.21 (1.00, 1.47) 0.045
≥35 years 100 (31.5) 84 (32.1) 0.98 (0.69, 1.39) 0.895 Basal T 0.025 0.875 1.02 (0.80, 1.29)
Late PL 114 (6.6) 49 (3.3) 2.11 (150, 3.00) <0.001 0.475 0.491 1.02 (0.97,1.07)
Basal A
<35 years 95 (6.8) 43 (3.5) 2.02 (1.40, 2.92) <0.001
≥35 years 19 (6.0) 6(2.3) 2.72 (1.07, 6.92) 0.036 Previous PL 0.003 0.956 0.96 (0.21, 4.40)
Ectopic Pregnancy 73 54 Primary infertility 0.465 0.495 0.80 (0.42,1.51)
Live birth 1113 (64.9) 1072 (71.6) 0.73 (0.63, 0.85) <0.001

Conclusion
 In women with PCOS undergoing IVF-ET, elevated BMI adversely affected late pregnancy loss but not early pregnancy loss.
Distinctive proteomic profiling and phenotypic correlations of plasma extracellular vesicles
provided clues for their regulatory roles in the pathogenesis of polycystic ovarian syndrome

Background
 Extracellular vesicles (EVs) from various tissues or body fluids have been shown to play a role in the pathogenesis of PCOS and may serve as
potential biomarkers for diagnosis and prognostic prediction.
 Most previous studies have focused on the expression of miRNAs in EVs isolated from blood, endometrium, and follicular fluid. A comprehensive
quantitative protein analysis of circulatory EVs in PCOS has rarely been conducted.
 It is also unclear whether and how the proteomic profiling of circulatory EVs is related to the characteristic phenotypic expression of PCOS.

Objective
 To elucidate the distinctive proteomic profiling of plasma extracellular vesicles (EVs) and their pathogenic contributions in polycystic ovary
syndrome (PCOS).

Methods
 This is a case-control study conducted at the Reproductive Endocrinology Department of a tertiary medical center from 2019 to 2022.
 Blood samples were collected from sixty PCOS patients and thirty non-PCOS control subjects.
 Plasma EVs were isolated using sucrose gradient-based ultracentrifugation.
 Quantitative proteomic analysis was conducted with tandem mass tag labeling and liquid chromatography-tandem mass spectrometry (TMT) to
identify differentially expressed proteins.
Distinctive proteomic profiling and phenotypic correlations of plasma extracellular vesicles
provided clues for their regulatory roles in the pathogenesis of polycystic ovarian syndrome

Results
 Nanoparticle tracking analysis suggested the majority of Evs were 70-190nm in diameter, which were corresponsive to the size of exosome.
 Differential expression protein (DEP) analysis revealed distinct upregulated proteins in the circulatory exosomes of PCOS patients, including IGF-1,
HIST1H1E, PF4, HBA1, HBB, and SNC73.
 These proteins were enriched in nitric oxide transport and negative regulation of extrinsic apoptotic signaling pathways.
 Proteins that were downregulated in PCOS patients, including RAA1, RARRES2, CFHR1, LBP, IGFBP3, TPI1, SERPINA5, and SNC73, were enriched in
lipid transport and complement and coagulation cascades.
 There is a significant correlation between the differentially expressed exosome proteins and several clinical phenotypes, including hypertension,
hyperandrogenism, and iron metabolism.
 The enriched pathways and characterized phenotypes have been shown to be closely related to the cardiovascular and metabolic abnormalities of
PCOS. This could provide pathogenic insights into how circulatory EV proteins contribute to the development and progression of the disease.

Conclusion
 In PCOS, the differentially expressed proteins in circulatory exosomes are associated with various signaling pathways related to cardiovascular and
metabolic risks.
Impact of low versus air oxygen tension on the oocyte maturation in PCOS women
undergoing capacitation IVM: a sibling oocyte pilot study

Background
 In vitro maturation (IVM) is an alternative assisted reproductive technology that reduces hormone-related side effects and the treatment burden for
patients.
 A novel biphasic in vitro maturation (IVM) method, known as capacitation IVM (CAPA-IVM), has enhanced oocyte competence, resulting in
successful live births.
 CAPA-IVM includes a pre-maturation phase with C-type natriuretic peptide (CNP) and a maturation phase with amphiregulin.
 Maturation rates using CAPA-IVM in PCOS patients are reported to be between 62% and 64.3%.

Objective
 To investigate the effectiveness of using low oxygen tension for both steps of CAPA-IVM culture.

Methods
 A pilot study on sibling oocytes was conducted from January 2023 to May 2024.
 Women aged 18–37 years, diagnosed with PCOS and undergoing CAPA-IVM, were recruited for the study.
 The cultivation of COCs took place in two benchtop incubators, each equipped with commercial mix-gas bottles to establish the respective oxygen
conditions.
Impact of low versus air oxygen tension on the oocyte maturation in PCOS women
undergoing capacitation IVM: a sibling oocyte pilot study

Results
 A total of 554 COCs from 20 eligible women were enrolled in the study (276 in the low oxygen group and 278 in the air oxygen group).
 The mean age of the participants was 31.4 ± 3.2 years, and the mean body mass index was 22.6 ± 2.5 kg/m².
 The number of mature oocytes and 2PN-fertilized oocytes was significantly lower in the low oxygen tension group compared to the air oxygen
tension group.
 Fifteen women underwent single blastocyst transfers, with six from the low oxygen group and nine from the air oxygen group.
 Clinical outcomes did not differ significantly between the two groups, and there were no multiple pregnancies in either group.
300
276 278 Low oxygen Air oxygen
100%
*P <0.05 Low oxygen Air oxygen
250 90%

200 80%
*183
70%
148
150 *133 60%
100 91 50%

46 40%
50 46
31 31 30%
8 14
0 20%
Total COCs Mature 2PN Biastocyst Good-quality Frozen
oocytes oocytes blastocyst blastocyst 10%
Positive Clinical Ongoing Miscarriage at
Embryology outcomes pregnancy test pregnancy pregnancy <12 weeks

Clinical outcomes

Conclusion
 In conclusion, a 5% oxygen tension during both steps of biphasic CAPA-IVM reduced the number of mature oocytes and 2PN fertilized oocytes compared
to a 20% oxygen tension. Further research is needed to determine the optimal oxygen concentration for each phase of CAPA-IVM.