1. Intern seminar Assisted reproductive technology and perinatal risk
Supervisor 謝旻玲醫師

2. Outline Case with congenital anomaly Discussion Introduction of ART
ART induced perinatal risk
Outcome of ART baby ART = Assisted reproductive technology 人工生殖技術
IVF = In Vitro Fertilization 體外人工受孕

3. Basic information - Name : 吳x融 - Age : 0 day-old - Chart No : 180XXX83
- Sex : male
- Admission : 2017/03/01

4. Chief complaint
- Prematurity 34 weeks with congenital heart disease and respiratory distress after birth

5. Mother hospital course
Prenatal examination at 奇美(IVF) ->
Twin A single umbilical artery
Twin B suspected fetus CHD (pregancy GA 23 weeks)
Cell-free DNA testing (NIPT): low risk trisomy 13,18,21
12/15
Right upper quadrant pain, susp. acute cholecystitis
Premature uterine contraction
Pre-eclampsia
02/06
02/13
Discharge

6. Mother hospital course
Abdominal pain, vaginal bleeding
Sent to NCKU ER -> admission
02/28
03/01
Caesarean section

7. Present illness Subcostal retraction,
air hunger without obvious cyanosis after birth

8. BP: 64/39 mmHg
Saturation: 90%
BP: 62/42 mmHg
Saturation: 86%
BP: 71/44 mmHg
Saturation:93%
BP: 80/53 mmHg
Saturation: 90%

9. Vital Signs :
T: 36.6°C
P: 158/min
R: 62/min
BP: 80/53mmHg
Chest :
Clear breath sound
No crackles,
Regular heart beats
Pansystolic murmur grade 2/6
Skin :
No petechiae or ecchymosis, hypospadias, imperforate anus

10. Past history - Birth History: - Growth and Development:
G1P1, C/S (twin, twin A breech), GA: 34+0 weeks, BBW:1598g, DOIC(-), PROM(-)
Apgar score: 7 -> 8
- Growth and Development:
BW: 1598g (3rd%, asymmetric SGA)
BH: 43.5cm (23th%)
HC: 30cm (15th%)

11. Family history
Mother:
Type 1 DM for 10++ years under insulin

12. Decreased lung marking
Decreasing lung marking

13. EKG
tall P waves, left axis deviation with a superior axis (>30°), LV hypertrophy, and diminished RV forces
Tall P-waves in lead II indicate right atrial enlargement, and ventricular forces are notable for left axis deviation and diminished right ventricular forces (small or absent R-waves in precordial leads V1–V3)

14. RV LV RA LA

15. LA RA LV
ASD RV

16. PA Ao
PA 前 AO 後 -> NO TGA

17. RV LV
RV hypoplasia

20. Lab data

21. Problem and plan
Tricuspid atresia, type 1B with pulmonary stenosis, VSD, large ASD and PDA, RV hypoplasia
6 m/o for 1st OP
Imperforate anus with cutaneous fistula
Consult pediatric surgeon for operation
Hypospadias with bilateral mild hydronephrosis
Consult urologist for operation (> 6 months)
- Prematurity 34 weeks

22. WHY ? Congenital anomaly
- IVF ?
- Maternal DM ?
- Chromosomal ?

23. Discussion Assisted reproductive technology and perinatal risk

24. Louise brown in 1978
- First ART baby - Oldham hospital

25. In Vitro Fertilization
Step 1: Control Ovarian Hyperstimulation (COH)
Step 2: Egg Retrieval 
Step 3: Fertilization
Step 4: Embryo Culture & Embryo Quality
Step 5: Embryo transfer
Assisted reproductive technologies (ART)代表所有在體外對oocyte做的事情。
其中，IVF是ART中的老祖宗，也是現今最常用的一種方式。
三步驟: 排蛋抓蛋受精蛋
排蛋Monitoring and stimulating a woman's ovulatory process
抓蛋Removing ovum or ova from the woman's ovaries
受精蛋Letting sperm fertilize them in a liquid in a laboratory.

26. In Vitro Fertilization
Factor which believed increase perinatal risk
underlying causes of infertility
- aspects of the ART procedures
the medications used,
culture media composition,
length of time in culture,
freezing and thawing of embryos,
altered hormonal environment at the time of implantation,
the manipulation of gametes and embryos or a combination of these.

27. Introduction Infertility 10-15% over world
(50% female, 30% male, 20% unknown)
ART induced perinatal risk
Preterm birth
LBW, SGA birth
Birth defect
Vertical transmission of genetic diseases ?

28. ART and Preterm birth
Statistically significant about 20% increase in the relative risk of preterm birth in IVF twins
Estimated two-fold increased risk of preterm birth in IVF singletons
Reason ?
McDonald SD, Han Z, Mulla S, Murphy KE, Beyene J, Ohlsson A. Preterm birth and low birth weight among in vitro fertilization singletons: a systematic review and meta-analyses. Eur J Obstet Gynecol Reprod Biol 2009;146:138–48

29. ART and LBW birth
Both singleton and twin IVF pregnancies demonstrate an increased risk of low birth weight compared with naturally conceived (RR about 1.5)
the relative risk of babies being SGA is also increased about 40–60%
McDonald SD, Han Z, Mulla S, Murphy KE, Beyene J, Ohlsson A. Preterm birth and low birth weight among in vitro fertilization singletons: a systematic review and meta-analyses. Eur J Obstet Gynecol Reprod Biol 2009;146:138–48

30. ART and Birth defect
Between 2% and 3% of all infants are diagnosed with a congenital anomaly soon after birth.
IVF is associated with a 30–40% increased risk of major congenital anomalies compared with natural conceptions.
pre-auricular tags, tongue tie,
undescended testicles, unstable hips,
single umbilical artery (
Hansen M, Bower C, Milne E, de Klerk N, Kurinczuk JJ. Assisted reproductive technologies and the risk of birth defects – a systematic review. Hum Reprod 2005;20:328–38

31. ART and Vertical transmission of genetic diseases
Microdeletions of the long arm of the Y chromosome (Yq), in particular the AZF region, can also cause spermatogenic failure and either oligo- or azoospermia
ART imprinting syndrome ???
Beckwith-Wiedemann syndrome (BWS), Angelman syndrome (AS) and, more recently, maternal hypomethylation syndrome
本科張旭陽、蔡孟穎醫師(1997年)曾針對68位南台灣的這些罹患無精子或精子稀少症的男性分析，發現有6位( 9%)的確有這方面基因的缺陷。 
Amor DJ, Halliday J. A review of known imprinting syndromes and their association with
assisted reproduction technologies

32. Long-term outcomes for children
The physical, neurological and developmental health of children born after IVF is normal
Cerebral palsy ???
Carson C, Kurinczuk JJ, Klemetti R, Redshaw M, et al. Cognitive development following ART: effect of choice of comparison group, confounding and mediating
factors. Hum Reprod 2010;25:244–52.

33. Long-term outcomes for children
ART parents - Expressed greater warmth towards their child,
- interacted more with their child
- less stress associated with parenting
Golombok S1, Brewaeys A, Cook R, Giavazzi MT, The European study of assisted reproduction families: family functioning and child development. Hum Reprod Oct;11(10):

34. Future
ART Technique WE

35. Take home message
IVF pregnancies are at increased risk of adverse perinatal outcomes, it is also the case that the majority of the children born following IVF will have a normal outcome
Recommend complete pre-natal examination for IVF birth

36. Reference
In Vitro Fertilisation: Perinatal Risks and Early Childhood Outcomes, Scientific Impact Paper No. 8 May 2012
Hansen M, Bower C, Milne E, de Klerk N, Kurinczuk JJ. Assisted reproductive technologies and the risk of birth defects – a systematic review. Hum Reprod 2012;20:328–38.
成大婦產部陳達生醫師

37. Thank you
ANY QUESTIONS ?

38. Brain echo showed mild PVE and follow-up brain echo showed normal on 03/16
He tried room air since 03/29 and able to use N/C, transferred to level 2 Advance feeding gradually, family train double-barrel colostomy care , MBD on 4/5