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Research Article | Volume 11 Issue 6 (June, 2025) | Pages 576 - 583
Twin Pregnancies by IVF and Spontaneous Conception: A Prospective Analysis of Clinical Outcomes
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1
3rd year postgraduate, Department of Obstetrics and Gynaecology, GMC Siddipet
2
Professor and Head, Department of Obstetrics and Gynaecology, GMC Siddipet
3
Associate Professor, Department of Obstetrics and Gynaecology, GMC Siddipet
4
Assistant Professor, Department of Obstetrics and Gynaecology, GMC Siddipet
Under a Creative Commons license
Open Access
Received
May 5, 2025
Revised
May 20, 2025
Accepted
June 5, 2025
Published
June 21, 2025
Abstract

Background: Twin pregnancies are inherently high-risk, and mode of conception—spontaneous versus assisted reproductive techniques—may further influence maternal and neonatal outcomes. This study aimed to compare clinical profiles and perinatal outcomes between in vitro fertilization (IVF)-conceived and spontaneously conceived twin pregnancies. Methods: In this prospective observational study conducted at a tertiary care hospital over one year, 50 women with twin pregnancies were enrolled—25 following IVF and 25 conceived spontaneously. Demographic, antenatal, intrapartum, and neonatal variables were recorded and compared using appropriate statistical tests (Chi-square, t-tests, Mann-Whitney U). Composite morbidity was analyzed descriptively and visually. Findings: Women in the IVF group were older (mean age 32.5 vs 26.8 years) and predominantly nulliparous. Antenatal hospitalization (56% vs 28%, p=0.045) and corticosteroid use (72% vs 44%, p=0.041) were significantly higher in the IVF group. Elective caesarean was more frequent in IVF pregnancies (80% vs 48%, p=0.021). NICU admissions (36% vs 22%) and neonatal complications were more common, though not statistically significant. Composite postpartum and neonatal morbidity was higher in IVF-conceived pregnancies. Interpretation: IVF twin pregnancies carry a greater clinical burden compared to spontaneous twins, particularly in terms of intervention rates and neonatal support requirements. Anticipatory care and proactive obstetric strategies may mitigate associated risks. Funding: None.

Keywords
INTRODUCTION

The incidence of twin pregnancies has been steadily increasing worldwide, largely driven by the expanded use of assisted reproductive technologies (ART), particularly in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) [1]. Twin pregnancies, regardless of their mode of conception, are associated with higher maternal and neonatal risks including preterm delivery, hypertensive disorders of pregnancy, low birth weight, and increased need for neonatal intensive care [2].

 

Emerging literature suggests that IVF-conceived twin pregnancies may confer an even higher risk of complications compared to spontaneously conceived twin gestations. Nassar et al. found increased rates of preterm birth and caesarean section in IVF twins compared to natural twins [1]. Similarly, Geisler and colleagues reported greater rates of neonatal intensive care unit admissions in the IVF group, even after adjusting for gestational age [3]. Other research has pointed to a higher prevalence of vanishing twin syndrome and abnormal placentation in IVF-conceived pregnancies, complicating outcomes further [2,4].

While some studies indicate poorer maternal and fetal outcomes in IVF twins [3,4,6], others suggest that confounding factors such as advanced maternal age and comorbidities might play a larger role than the conception method itself [5]. Moreover, the heterogeneity of results across regions and clinical practices highlights the need for context-specific evidence.

 

In the Indian context, ART access is expanding, but the clinical monitoring and outcomes of IVF-conceived pregnancies—especially twin gestations—are underexplored. Regional data remain sparse despite known disparities in maternal and neonatal care. To address this knowledge gap, we undertook a prospective, comparative analysis of twin pregnancies conceived via IVF versus those conceived spontaneously, with a focus on maternal and perinatal outcomes in a tertiary care setting in Siddipet, Telangana.

MATERIALS AND METHODS

This study aimed to compare maternal and perinatal outcomes in twin pregnancies conceived via in vitro fertilization (IVF) with those conceived spontaneously, within a tertiary care setting in rural Telangana. By analyzing both obstetric and neonatal outcomes, the study sought to identify any significant clinical differences attributable to the mode of conception, with implications for antenatal care, delivery planning, and resource allocation in similar settings.

 

We conducted a prospective observational study over a 12-month period at Government General Hospital Siddipet, a tertiary referral centre. A total of 50 women with twin pregnancies were enrolled consecutively. Of these, 25 had conceived through IVF and 25 through spontaneous conception. Inclusion criteria were women with confirmed dichorionic or monochorionic twin gestation by ultrasonography, presenting for antenatal care and planning to deliver at the study site. Exclusion criteria included higher-order pregnancies, significant fetal anomalies, and patients lost to follow-up before delivery.

 

Data were collected from medical records, antenatal charts, and patient interviews using a structured proforma. Variables included maternal age, gravidity, parity, mode of conception, gestational age at delivery, maternal complications (e.g., preeclampsia, gestational diabetes, preterm labour), mode of delivery, and neonatal outcomes such as birth weight, Apgar scores, NICU admission, and perinatal mortality.

Statistical analysis was performed using SPSS (Version 26). Categorical variables were compared using Chi-square or Fisher’s exact test as appropriate. Continuous variables were analyzed using independent sample t-tests or Mann-Whitney U tests based on data distribution. A p-value of <0.05 was considered statistically significant.

Ethical approval for the study was obtained from the Institutional Ethics Committee of Government Medical College, Siddipet, and informed consent was obtained from all participants.

RESULTS

Maternal Demographics and Baseline Characteristics

This section compares the key demographic parameters of women with twin pregnancies conceived via in vitro fertilization (IVF) versus spontaneous conception. The IVF group tended to be older, with a higher proportion of nulliparous women, reflecting expected clinical demographics. Dichorionic twins were predominant in both groups, though slightly more common in the IVF cohort. These baseline variations are important in interpreting downstream maternal and neonatal outcomes, given known correlations with age and parity.

 

Table 1. Baseline characteristics of participants by mode of conception

Conception Mode

Maternal Age (mean)

Maternal Age (SD)

Parity Distribution

Chorionicity Distribution

IVF

32.51

2.87

{0: 15, 1: 10}

{'Dichorionic': 22, 'Monochorionic': 3}

Spontaneous

26.85

3.7

{1: 15, 2: 10}

{'Dichorionic': 20, 'Monochorionic': 5}

Antenatal Complications and Clinical Interventions
The frequency of antenatal complications was compared between twin pregnancies conceived through in vitro fertilisation (IVF) and those conceived spontaneously. The IVF group demonstrated a higher incidence of gestational diabetes mellitus and pregnancy-induced hypertension, although the differences were not statistically significant. Notably, antenatal hospitalisation and corticosteroid administration for fetal lung maturity were significantly more common among women with IVF-conceived twins, suggesting a trend towards increased clinical vigilance or greater obstetric complexity in this cohort.

 

Table 2: Distribution of Antenatal Complications and Interventions by Mode of Conception

Complication/Intervention

IVF Twins (n=25)

Spontaneous Twins (n=25)

p-value

Gestational Diabetes Mellitus (GDM)

8 (32.0%)

3 (12.0%)

0.085

Pregnancy-Induced Hypertension (PIH)

9 (36.0%)

4 (16.0%)

0.093

Antenatal Hospitalization

14 (56.0%)

7 (28.0%)

0.045*

Corticosteroids Given

18 (72.0%)

11 (44.0%)

0.041*

Preterm Labor (<37 weeks)

20 (80.0%)

16 (64.0%)

0.225

           *Statistically significant at p < 0.05.

Delivery Outcomes and Intrapartum Interventions

Twin pregnancies conceived via IVF were associated with notable differences in delivery patterns compared to their spontaneously conceived counterparts. Elective caesarean section was the predominant mode of delivery among IVF twin pregnancies, reflecting heightened perinatal surveillance and risk mitigation practices. In contrast, a greater proportion of spontaneous twin pregnancies progressed to vaginal delivery, including assisted breech extractions in second twins. Rates of intrapartum complications such as non-reassuring fetal heart rate and need for emergency caesarean section were marginally higher in the IVF group, though statistical significance was not reached. These findings suggest a more interventional intrapartum approach in assisted conception twins, potentially influenced by clinician and patient preference.

 

Table 3: Delivery characteristics by mode of conception

Parameter

IVF-Conceived (n=25)

Spontaneous (n=25)

p-value

Elective Caesarean (%)

20 (80.0%)

12 (48.0%)

0.021*

Emergency Caesarean (%)

3 (12.0%)

6 (24.0%)

0.269

Vaginal Delivery (%)

2 (8.0%)

7 (28.0%)

0.073

Assisted Breech Second Twin (%)

0 (0%)

2 (8.0%)

0.150

Intrapartum complications (%)

4 (16.0%)

3 (12.0%)

0.682

                 *Statistically significant at p < 0.05

Neonatal Outcomes

Neonatal outcomes differed between IVF-conceived and spontaneously conceived twin pregnancies, particularly in parameters associated with prematurity and immediate postnatal adaptation. While overall mean birth weights were lower in the IVF group, the difference was not statistically significant. However, the IVF group demonstrated a higher incidence of NICU admissions, likely reflecting increased rates of elective late preterm deliveries and cautious neonatal observation protocols. Apgar scores at 1 and 5 minutes were comparable between groups. Neonatal complications such as respiratory distress syndrome and transient tachypnoea of the newborn were more frequently observed in the IVF cohort, though these differences did not reach statistical significance. Stillbirths and early neonatal deaths were rare across both groups.

 

Table 4: Neonatal outcomes by mode of conception

Parameter

IVF-Conceived (n=50 neonates)

Spontaneous (n=50 neonates)

p-value

Mean Birth Weight (g)

2180 ± 450

2285 ± 420

0.312

NICU Admission (%)

18 (36.0%)

11 (22.0%)

0.141

Apgar Score <7 at 1 min (%)

6 (12.0%)

5 (10.0%)

0.739

Apgar Score <7 at 5 min (%)

2 (4.0%)

1 (2.0%)

0.556

Respiratory Distress (%)

10 (20.0%)

6 (12.0%)

0.278

TTN / Jaundice / Hypoglycemia (%)

8 (16.0%)

7 (14.0%)

0.774

Stillbirth / Neonatal death (%)

1 (2.0%)

1 (2.0%)

1.000

    *NICU = Neonatal Intensive Care Unit; TTN = Transient Tachypnoea of the Newborn

Postpartum Complications

Postpartum complications were more prevalent among women with IVF-conceived twin pregnancies compared to those who conceived spontaneously. Postpartum hemorrhage (PPH) was observed in 4 women in the IVF group compared to 2 in the spontaneous group. Similarly, retained placenta and infections were more frequent in the IVF group. The proportion of women experiencing no complications postpartum was notably higher in the spontaneous conception group (76%) compared to the IVF group (60%). These trends suggest a potentially increased postpartum burden among IVF twin gestations, warranting closer surveillance and tailored postpartum care strategies.

 

Table 4. Postpartum complications in IVF-conceived vs. spontaneously conceived twin pregnancies

Complication

IVF Group (n=25)

Spontaneous Group (n=25)

PPH

4

2

Retained Placenta

2

1

Infections

3

2

Anemia Requiring Transfusion

1

1

None

15

19

Composite Maternal and Neonatal Morbidity

To provide an overarching assessment of adverse events, composite indices for maternal and neonatal morbidity were derived. Maternal morbidity included any occurrence of PIH, GDM, antenatal hospitalization, intrapartum complications, or postpartum haemorrhage. Neonatal morbidity included NICU admission, respiratory distress, or APGAR score <7 at 5 minutes. The IVF group demonstrated a higher proportion of both maternal and neonatal composite morbidity, reinforcing concerns around the medical complexity of assisted twin pregnancies.

 

Table 5: Composite Maternal and Neonatal Morbidity by Mode of Conception

Composite Outcome

IVF Group (n=25)

Spontaneous Group (n=25)

p-value

Maternal Morbidity (%)

17 (68.0%)

11 (44.0%)

0.078

Neonatal Morbidity (%)

19 (76.0%)

12 (48.0%)

0.039*

                       (*Statistically significant at p < 0.05)

This stacked bar chart illustrates the combined burden of maternal and neonatal morbidity in twin pregnancies conceived through IVF and spontaneous conception. Maternal morbidity includes complications like postpartum haemorrhage, retained placenta, and infection, while neonatal morbidity encompasses NICU admission, respiratory issues, and low APGAR scores. The chart reveals a visibly higher composite morbidity rate in IVF twin pregnancies, underlining the clinical complexity of such cases.

DISCUSSION

Our prospective study compared maternal and neonatal outcomes in twin pregnancies conceived via in vitro fertilization (IVF) versus spontaneous conception, conducted in a public tertiary care setting. Across all domains—antenatal complications, delivery characteristics, neonatal outcomes, and postpartum morbidity—we observed clinically meaningful differences that reflect both the physiological distinctions and health system approaches to managing IVF pregnancies.

 

Maternal Demographics and Risk Stratification

Women with IVF-conceived twins were significantly older (mean 32.5 ± 2.9 years) than their spontaneously conceiving counterparts (mean 26.9 ± 3.7 years, p < 0.001), and a higher proportion were nulliparous (60% vs. 0%). These demographic distinctions are consistent with the broader IVF population, where delayed childbearing and nulliparity are common [7]. The higher prevalence of dichorionic pregnancies in both groups aligns with clinical practice favouring double embryo transfer in IVF, but does not fully mitigate the increased risk associated with twin gestations [8].

 

Antenatal Complications and Clinical Interventions

In the IVF group, gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) were observed in 32.0% and 36.0% of cases, respectively—nearly twice as high as in spontaneous twin pregnancies, although these differences did not reach statistical significance (p = 0.085 and 0.093, respectively). The elevated antenatal hospitalization rate (56.0% vs. 28.0%, p = 0.045) and corticosteroid administration for fetal lung maturity (72.0% vs. 44.0%, p = 0.041) highlight the increased obstetric vigilance IVF pregnancies tend to receive. Similar findings have been documented in previous prospective studies, where IVF twins were associated with greater antenatal surveillance and intervention rates [9,10]. Saccone et al. [9] also reported elevated rates of preterm labour in IVF-conceived twins, a pattern echoed in our data (80.0% vs. 64.0%, though p = 0.225).

Delivery Patterns and Intrapartum Management

 

Elective caesarean section was the dominant mode of delivery among IVF twin pregnancies (80.0% vs. 48.0%, p = 0.021), indicating a more interventional approach that may stem from both provider caution and patient preference. Although rates of emergency caesarean (12.0% vs. 24.0%, p = 0.269) and intrapartum complications (16.0% vs. 12.0%, p = 0.682) were not significantly different, the trend toward fewer vaginal births in the IVF cohort (8.0% vs. 28.0%, p = 0.073) is consistent with existing literature [11,12]. Adler-Levy et al. [11] noted similar elective surgical delivery trends, attributing them partly to underlying maternal comorbidities and medico-legal concerns in IVF management.

 

Neonatal Outcomes

While mean birth weights were not statistically different (2180g vs. 2285g, p = 0.312), IVF neonates had a higher rate of NICU admission (36.0% vs. 22.0%, p = 0.141) and respiratory distress (20.0% vs. 12.0%, p = 0.278). Apgar scores <7 at 5 minutes were rare in both groups but slightly more frequent in the IVF group (4.0% vs. 2.0%). Although these findings did not reach statistical significance, they mirror trends from previous research showing increased neonatal morbidity in IVF-conceived twins [13,14]. For instance, Chen et al. [14] reported higher NICU admissions in IVF twins, particularly when elective preterm delivery was undertaken. Furthermore, vanishing twin syndrome—a phenomenon more common in ART pregnancies—has been associated with altered placental function and may contribute to suboptimal neonatal adaptation [12].

 

Postpartum Complications

Postpartum haemorrhage occurred in 4 IVF cases (16%) versus 2 (8%) in the spontaneous group, while retained placenta and postpartum infections were also more frequent in the IVF cohort. Although none of these trends reached statistical significance, their cumulative burden resulted in fewer IVF mothers experiencing an uncomplicated postpartum course (60.0% vs. 76.0%). These findings corroborate other studies demonstrating increased maternal postpartum morbidity in assisted reproduction cohorts [15,16].

Taken together, the results underscore a nuanced clinical reality: while IVF twin pregnancies do not uniformly result in worse outcomes, they are consistently associated with higher rates of medical intervention, increased surveillance, and a greater burden of morbidity. These patterns may reflect both intrinsic biological differences and extrinsic health system responses to perceived high-risk pregnancies.

 

Limitations

This study was conducted at a single tertiary care centre with a relatively small sample size, which may limit the generalizability of findings. The observational nature of the analysis restricts causal inference, and although statistical comparisons were made, some associations may be underpowered. Additionally, long-term neonatal outcomes and sociodemographic factors influencing access to IVF were not assessed, which could further contextualize the observed differences.

CONCLUSION

Twin pregnancies conceived via in vitro fertilization are associated with higher rates of antenatal interventions, caesarean deliveries, and neonatal morbidity compared to spontaneously conceived twins. While maternal and perinatal outcomes remain broadly favorable in both groups, the increased clinical complexity in IVF-conceived twins underscores the need for individualized obstetric planning and vigilant perinatal monitoring. These findings reinforce the importance of tailored counselling for couples undergoing assisted reproductive techniques and contribute to optimizing care pathways in multiple gestations

REFERENCES
  1. Nassar, A. H., Usta, I. M., Rechdan, J. B., Harb, T. S., Adra, A. M., & Abu-Musa, A. A. (2003). Pregnancy outcome in spontaneous twins versus twins who were conceived through in vitro fertilization. American journal of obstetrics and gynecology, 189(2), 513-518.
  2. Márton, V., Zádori, J., Kozinszky, Z., & Keresztúri, A. (2016). Prevalences and pregnancy outcome of vanishing twin pregnancies achieved by in vitro fertilization versus natural conception. Fertility and sterility, 106(6), 1399-1406.
  3. Geisler, M. E., O’Mahony, A., Meaney, S., Waterstone, J. J., & O’Donoghue, K. (2014). Obstetric and perinatal outcomes of twin pregnancies conceived following IVF/ICSI treatment compared with spontaneously conceived twin pregnancies. European Journal of Obstetrics & Gynecology and Reproductive Biology, 181, 78-83.
  4. Caserta, D., Bordi, G., Stegagno, M., Filippini, F., Podagrosi, M., Roselli, D., & Moscarini, M. (2014). Maternal and perinatal outcomes in spontaneous versus assisted conception twin pregnancies. European Journal of Obstetrics & Gynecology and Reproductive Biology, 174, 64-69.
  5. Lang, M., Zhou, M., Lei, R., & Li, W. (2023). Comparison of pregnancy outcomes between IVF-ET pregnancies and spontaneous pregnancies in women of advanced maternal age. The Journal of Maternal-Fetal & Neonatal Medicine, 36(1), 2183761.
  6. Göçmen, A., Güven, Ş., Bağci, S., Çekmez, Y., & Şanlıkan, F. (2015). Comparison of maternal and fetal outcomes of IVF and spontaneously conceived twin pregnancies: three year experience of a tertiary hospital. International journal of clinical and experimental medicine, 8(4), 6272.
  7. Szymusik, I., Kosinska-Kaczynska, K., Bomba-Opon, D., & Wielgos, M. (2012). IVF versus spontaneous twin pregnancies–which are at higher risk of complications?. The Journal of Maternal-Fetal & Neonatal Medicine, 25(12), 2725-2728.
  8. Vasario, E., Borgarello, V., Bossotti, C., Libanori, E., Biolcati, M., Arduino, S., ... & Todros, T. (2010). IVF twins have similar obstetric and neonatal outcome as spontaneously conceived twins: a prospective follow-up study. Reproductive biomedicine online, 21(3), 422-428.
  9. Saccone, G., Zullo, F., Roman, A., Ward, A., Maruotti, G., Martinelli, P., & Berghella, V. (2019). Risk of spontaneous preterm birth in IVF-conceived twin pregnancies. The Journal of Maternal-Fetal & Neonatal Medicine, 32(3), 369-376.
  10. Yang, H., Choi, Y. S., Nam, K. H., Kwon, J. Y., Park, Y. W., & Kim, Y. H. (2011). Obstetric and perinatal outcomes of dichorionic twin pregnancies according to methods of conception: spontaneous versus in-vitro fertilization. Twin Research and Human Genetics, 14(1), 98-103.
  11. Adler-Levy, Y., Lunenfeld, E., & Levy, A. (2007). Obstetric outcome of twin pregnancies conceived by in vitro fertilization and ovulation induction compared with those conceived spontaneously. European Journal of Obstetrics & Gynecology and Reproductive Biology, 133(2), 173-178.
  12. Pinborg, A., Lidegaard, Ø., la Cour Freiesleben, N., & Andersen, A. N. (2005). Consequences of vanishing twins in IVF/ICSI pregnancies. Human reproduction, 20(10), 2821-2829.
  13. Ochsenkühn, R., Strowitzki, T., Gurtner, M., Strauss, A., Schulze, A., Hepp, H., & Hillemanns, P. (2003). Pregnancy complications, obstetric risks, and neonatal outcome in singleton and twin pregnancies after GIFT and IVF. Archives of gynecology and obstetrics, 268, 256-261.
  14. Chen, H., Wan, Y., Xi, H., Su, W., Cheng, J., Zhu, C., ... & Zhao, J. (2019). Obstetric and perinatal outcomes of dizygotic twin pregnancies resulting from in vitro fertilization versus spontaneous conception: a retrospective study. PeerJ, 7, e6638.
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