INTRODUCTION: Infertility, a reproductive health condition prevalent among one in every four couples in the developing countries, is a neglected problem.In this era of exponential industrialization and global changes, lifestyle disorders like infertility are on the ri se. It is estimatedthat infertility affects 8 to 12 per cent of couples worldwide. overall IVF pregnancies are often seen as risky mainly due to multiple gestations. However, even singletonART pregnancies are associated with increased incidences of preterm birth, low birth weight, small-for-gestational-age (SGA) infants, and obstetric complications such as preeclampsia, placental abruption, and placenta praevia. While there are many studies that compare pregnancies after assisted reproductive techniques with spontaneously conceived pregnancies, fewer data are available that evaluate the differences between IVF and ICSI-conceived pregnancies. The aim of our study was to compare adversepregnancy outcomes in IVF and ICSI cases and how they vary depending on age factor.

METHODS: This retrospective cohort study was conducted at Radhakrishna multispeciality hospital and IVF center, Bangalore during January 2013 to January 2019. A total of 667 of which 434 were IVF and 233 ICSI cases were done. 263 cases were pregnancy positive out of which 149cases underwent conventional IVF and 114 cases underwent ICSI. These cases were divided into three groups depending upon age factor. Outcome variables included maternal parameters: i.e., age; gravity;duration of infertility, pregnancy complications such as abortions, ectopic pregnancy, multiple pregnancies, pregnancy-induced hypertension, preeclampsia, prematurerupture of membranes, gestational diabetes mellitus, IUGR and preterm labour; antepartum hemorrhage and fetal parameters: i.e., gestational age; low and very low birth weight,meconium aspiration syndromeand need for NICU admission.

RESULTS: In the study among those who had IVF pregnancy, there was no significant association between causes and Age distribution. however, a greater number of ICSI cases were done for male factor infertility. In IVF group, there was significant difference in Biochemical Pregnancy, Gestational DM, Pre-Term Labour, Oligo Hydramnios and Poly Hydramnios with respect to age distribution. I.e., all the above-mentioned complications were significantly high in mothers in the age group 30 to 40 years compared to other age groups. There was no significant difference in other complications with respect to age distribution. In ICSI group, there was significant difference in Biochemical Pregnancy with respect to age distribution. I.e., Biochemical Pregnancy were significantly high in mothers in the age group 30 to 40 years compared to other age groups. In the study there was significant difference in Preterm birth and NICU admission in IVF group with respect to age distribution. I.e., Preterm birth and NICU admission were highest in the age group 30 to 40 years mother.

CONCLUSION: Women who conceived with IVF and ICSI were at higher risk of maternal and perinatal complications particularly with age group 30-40 years. There was significant increase in multiple pregnancies, gestational diabetes and preterm labour and NICU admission in IVF group. Hence with proper diagnosis, stimulation protocol and with single embryo transfer can reduce the risk of multiple birthand further perinatal complications.

Infertility, a reproductive health condition prevalentamong one in every four couplesin the developing countries, is a neglected problem. In this era of exponential industrialization and global changes, lifestyle disorders like infertility are on the rise. It is estimated that infertility affects 8 to 12 per cent of couples worldwide [1]. In India, the overall prevalence of primary infertility varies from 3.9 to 16.8 per cent.[2]. Assisted reproductive technologies (ART) such as in vitro fertilization (IVF)and intracytoplasmic sperm injection (ICSI) have emerged as a promising treatment option for infertility.The obvious goals of all such treatments are to achieve a pregnancy and subsequent birth of a healthy infant, but overall IVF pregnancies are often seen as risky mainly due to multiple gestations. However, even singleton ART pregnancies are associated with increased incidences of pretermbirth, low birth weight, small-for-gestational-age (SGA) infants, and obstetric complications such as preeclampsia, placental abruption, and placenta praevia.[3][4] While there are many studiesthat compare pregnancies after assisted reproductive techniques with spontaneously conceived pregnancies, fewer data are available that evaluate the differences between IVF and ICSI-conceived pregnancies. The aim of our study was to compare adverse pregnancy outcomes in IVF and ICSIcases and how they vary depending on age factor.

This retrospective cohort study was conducted at Radhakrishna multispeciality hospital and IVF center, Bangalore during January 2013 to January 2019. A total of 667 of which 434 were IVF and 233 ICSI cases were done. 263 cases were pregnancy positiveout of which 149cases underwent conventional IVF and 114 cases underwent ICSI. These cases were divided into three groups depending upon age factor. Patients who were used donor egg/ semen / embryo were excluded from the study group. The aetiology in each case was diagnosed with ultrasonography, laboratory parameters, hysterolaparoscopy (when appropriate) and sperm analysis was done in all couples. Unexplained infertility was defined as infertility lasting atleast one year for which no explanatory factor was identified. The pregnancies and deliveries of the study and reference groups were handled in the same hospital,and ART treatments were carriedout in the same unit.

Outcome variables includedmaternal parameters: i.e., age; gravity;duration of infertility, pregnancy complications such as abortions, ectopic pregnancy, multiple pregnancies, pregnancy- induced hypertension, preeclampsia, premature rupture of membranes, gestational diabetes mellitus, IUGR and preterm labour;antepartum hemorrhage and fetal parameters: i.e., gestational age; low and very low birth weight, meconiumaspiration syndrome and need for NICU admission.

Statistical analysis:

Data was entered into Microsoft excel data sheet and was analyzed using SPSS 22 version software. Categorical data was represented in the form of Frequencies and proportions. Chi-square test was used astest of significance for qualitative data.

Graphical representation of data: MS Excel and MS word was used to obtain various types of graphs such as bar diagram.

p value (Probability that the result is true) of <0>

Statistical software: MS Excel, SPSS version 22 (IBM SPSS Statistics, Somers NY, USA) was used to analyze data. [5][6]

total of 667 patients underwent IVF/ICSI during six-year period between January 2013 to January 2019. Out of these cases pregnancypositive were 263. Of them 63%(149cases) by IVF and 43.3% (114 cases) by ICSI. In the study among subjects in the age group 20 to 30 years, 57.7% had pregnancy by IVF and 49.1% by ICSI. Among subjects in the age group 30 to 40 years, 39.5% had pregnancy by IVF and 44.7% by ICSI. There was no significant association between age and type of pregnancy.

χ 2 =3.136, df =2, p =0.208

Duration of Infertility with respect to age distribution in IVF and ICSI group

In the study among those who had IVF and ICSI pregnancy, no significant association was observed between duration of fertility and age distribution. Highest IVF and ICSI pregnancies were observed in the subjectsaged between 30 to 40 years with 5 to 10 years of durationof fertility.

Type of Infertility with respect to age distribution in IVF and ICSI group

In the study among subjects who had IVF pregnancy, there was no significant association between Type of Infertility and Age distribution. Similarly, among subjects who had ICSI pregnancy, there was no significant association between Type of Infertility and Age distribution.

Causes with respect to age distribution in IVF and ICSI group

In the study among those who had IVF pregnancy, there was no significant association between causes and Age distribution. however, a greater number of ICSI cases were done for male factor infertility

: Complications in Pregnancy with respect to age distribution in IVF and ICSI group

In IVF group, there was significant difference in Biochemical Pregnancy, Gestational DM, Pre-Term Labour, Oligo Hydraminos and Poly Hydraminos with respect to age distribution. I.e., all the above-mentioned complications were significantly high in mothers in the age group 30 to 40 years compared to other age groups.

There was no significant difference in other complications with respect to age distribution. In ICSI group, therewas significant difference in Biochemical Pregnancywith respect to age distribut ion.

I.e., Biochemical Pregnancywere significantly high in mothers in the age group 30 to 40 years compared to other age groups.

There was no significant difference in other complications with respect to age distribution.

Outcome in Pregnancy with respect to age distribution in IVF and ICSI group

In the IVF group, there was significant difference in Preterm labour, LSCS elective surgery with respect to age distribution. I.e., Preterm labour and Elective LSCS was significantly high in 30 -40 years Motherscompared to other age group.

There was no significant difference in FTND, EmergencyLSCS, Vacuum and Forceps delivery.

In ICSI group, there was significant difference in Emergency LSCS with respectto age distribution.

I.e., Emergency LSCS was significantly high in 30-40 years Motherscompared to otherage group.

There was no significant difference in Preterm Labour,FTND, Elective LSCS, Vacuum and Forceps delivery.

Neonatal Outcomewith respect to age distribution in IVF and ICSI group

In the study there was significant difference in Preterm birth and NICU admission in IVF group with respect to age distribution. I.e., Preterm birth and NICU admission were highest in the age group 30 to 40 years mothers respectively.

There was no significant difference in LBW, ELBW and MAP in IVF group with respect to age distribution.

Sex of New born with respect to age distribution in IVF and ICSI group

χ 2 =2.152, df =1, p =0.142

In the study there was no significant association between type of pregnancy and gender of new- born. In IVF group, majority of new-borns was female and in ICSI group majoritywere males.

The number of pregnancies after ART is still increasing and there is some data showing that IVF/ICSIis associated with a higher rate ofcomplications with regard to both the course of pregnancy and neonatal outcome. Of note, the potential negative impact of micromanipulation techniques should be considered, but only a few research studies have made precise distinctions between IVF and ICSI pregnancies.

Total of 667 patients underwent IVF/ICSI during six-year period between January 2013 to January 2019. Out of these cases pregnancypositive were 263. Of them 63%(149cases) by IVF and 43.3% (114 cases) by ICSI. In the study among subjects in the age group 20 to 30 years, 57.7% had pregnancy by IVF and 49.1% by ICSI. Among subjects in the age group 30 to 40 years, 39.5% had pregnancy by IVF and 44.7% by ICSI. There was no significant association between age and type of pregnancy. In IVF group, there was significant difference in Biochemical Pregnancy, Gestational DM, Pre-Term Labour, Oligo Hydraminos and Poly Hydraminoswith respect to age distribution.

I.e., all the above-mentioned complications were significantly high in mothers in the age group 30 to 40 years compared to other age groups. There was no significant difference in other complications with respect to age distribution. In ICSI group, there was significant difference in Biochemical Pregnancy with respect to age distribution. I.e. Biochemical Pregnancy were significantly high in mothers in the age group 30 to 40 years compared to other age groups.There was no significant difference in other complications with respect to age distribution. There was increase in incidence of multiple pregnancies with IVF group although it was not statistically significant when comparedwith age groups.

In a study done by Thompson F et.al [7] compared pregnancies with ART and normal population showed a twofold increased risk of preeclampsia, gestational diabetes, caesarean rates and increased risk of abruption and placenta previa. Study done by Gunby et al [8] rate of multiple pregnancies with IVF is 30% by the Canadianassisted reproductive technologies register.

In the IVF group, there was significant difference in Preterm labour, LSCS elective surgery with respect to age distribution. I.e., Preterm labour and Elective LSCS was significantly high in 30 -40 years Motherscompared to other age group. There was no significant difference in FTND, Emergency LSCS, Vacuum and Forceps delivery. In ICSI group, there was significant difference in Emergency LSCS with respect to age distribution. I.e., Emergency LSCS was significantly high in 30-40 years Mothers compared to other age group. There was no significant difference in Preterm Labour, FTND, Elective LSCS,Vacuum and Forceps delivery.

According to et.al Fechner et.alstudy, production of high levels of steroid hormones and other protein peptides resulting from ovarian stimulation increases risk of preterm deliveries. A meta-analysis in literature also showed that singleton pregnancies through IVF/ICSI after single our double embryo transfer are 1.8-2.1 times more prone to risk of preterm deliveries compared with spontaneously conceived pregnancies.[9]

In the study there was significant difference in Preterm birth and NICU admission in IVF group with respect to age distribution. I.e., Preterm birth and NICU admission were highest in the age group 30 to 40 years mothers respectively. There was no significant difference in LBW, ELBW and MAP in IVF group with respect to age distribution. A recent study done by Gibbsons et.al Society for assisted reproductive technology report comparing 60,037 standard IVF cases with 10,176 donor egg and 1,180 gestational carriers found that increased risk of low birth weight, preterm, and extremely low birth babiesin IVF cycles [10].

Women who conceivedwith IVF and ICSI were at higher risk of maternal and perinatal complications particularly with age group 30-40 years. There was significant increase in multiple pregnancies, gestational diabetes and preterm labour and NICU admission in IVF group. Hence with proper diagnosis, stimulation protocol and with single embryo transfer can reduce the risk of multiple birthand further perinatalcomplications pertaining to advanced age factor.