1. IVM IVF/ICSI nin YERİNİ ALACAK MI ?
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Prof Dr Bülent GÜLEKLİ
Dokuz Eylül Üniversitesi Tıp Fakültesi
Kadın Hastalıkları ve Doğum ABD Başkanı
Reprodüktif Endokrinoloji ve IVF
Bilim Dalı Öğretim Üyesi

2. Cumulative conception rate (%)
n: 4777 IVF cycles
Cumulative conception rate (%)
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Today in vitro fertilization and embryo transfer is an established and successful form of treatment for infertility.
It has been reported that for women below 34 years old the cumulative pregnancy and live birth rate after 3 cycles of IVF treatment were 63 and 61 percent respectively. These data suggest that pregnancy and live birth rates may actually be higher after IVF than natural conception in fertile couples.
Such those high success rates with IVF are achieved by replacing more than one embryo which requires to get plenty oocytes
Number of cycles / month
Tan et.al Lancet 1990

3. IVF treatment with ovarian stimulation
Ovarian stimulation with protocols involving GnRH agonist or antagonist in combination with gonadotrophins
More oocytes available for insemination
Success rates related to the number of embryos available for transfer
Initially designed for tubal factor infertility, but currently used for other indications
Good pregnancy rates
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4. Early studies on IVM of human oocytes
Rock and Menkin (1944): Science, 100:
Edwards (1965): Nature, 208:
- matured human oocytes from antral follicles
Kennedy and Donahue (1969): Science,
164:
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‘An alternative to the hyperstimulatory techniques is oocyte-maturation in-vitro’ – John Eppig (1989, Nat. Acad. Sci.)

5. Immature oocytes from unstimulated ovaries (Egg donation)
Cha et al. (1991): Fertil. Steril., 55: – birth of healthy twins
Cha et al. (1992): Reprod. Fertil. Dev., 4:
Hwang et al. (1997): Fertil. Steril., 68:
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6. Immature oocytes from unstimulated ovaries (Oocytes from natural cycles)
Paulson et al. (1992): Fertil. Steril., 57:
Paulson et al. (1994): Hum. Reprod., 9:
Thornton et al. (1998): Fertil. Steril., 70:
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7. Development of the follicle
Follicular growth
Stage Follicular size (mm)
Primordial –
Primary –
Secondary –
Preantral –
Early antral –
Antral – 16.00
Preovulatory – 20.00
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Gougeon, A. (1986): Hum. Reprod., 1:81-87.

8. Why IVM is an alternative treatment option?
Recovery of immature oocytes followed by IVM is a potentially useful treatment for patients with infertility
Women with polycystic ovaries (PCO) or polycystic ovarian syndrome (PCOS) have a slightly higher risk of developing ovarian hyperstimulation syndrome (OHSS)
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9. Advantages of IVM for infertile patients
Avoidance of side effects resulting from gonadotrophin stimulation, including OHSS
To simplify treatment, especially for the women
Reduced cost
Rescue early follicles
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10. Selection criteria for IVM patients
Patients with PCO or PCOS, irregular or regular-cycling
Antral follicle count (AFC) >20
Age <35 years
4. ‘IVM is suitable for patients with normal ovaries; suitable for MF and Unexp patients’ - acceptable preg. rates (Suikkari, Finland)
5. Other (previous poor response to IVF, oocyte donation and fertility preservation for cancer patients)
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11. Clinical preparation of patients for IVM
Protocol 1
(no stimulation)
ET (day 3)
U/S OR
ICSI
hCG
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U/S
rFSH 150IU/day OR
ICSI ET
Protocol 2 (stimulation)

12. IVM oocyte retrieval Oocyte retrieval 36 hrs after hCG injection
Performed under general anesthesia
Oocyte aspiration as per standard IVF, aspiration pressure 7.5 – 8.0 KPa (85 – 100 mm Hg) using Cook aspiraton needle.
3 – 4 follicles aspirated, one after another
Follicular fluid collected in tubes containing 2 ml of warm heparinised saline soln. (heparin 2 IU/ml). The needle is then flushed with warm heparinised saline
Tube containing aspirate is handed to the embryologist
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13. McGill Reproductive Center, Royal Victoria Hospital
Priming with hCG before retrieval of immature oocytes in women with infertility due to polycystic ovary syndrome
Chian RC, Gülekli B, Buckett WM, Tan SL
McGill Reproductive Center, Royal Victoria Hospital
Montreal, Canada
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N Engl J Med 1999; 341:

14. SLIDE 6 Standart ART Cycle

15. Chian RC et al., Hum Reprod 15: 165-170, 2000
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Chian RC et al., Hum Reprod 15: , 2000

16. McGill Reproductive Center, Royal Victoria Hospital, Montreal, Canada
Randomized, controlled trial of priming with 10,000 IU versus 20,000 IU of human chorionic gonadotropin in women with polycystic ovary syndrome who are undergoing in vitro maturation
Gulekli B, Buckett WM, Chian RC, Child TJ, Abdul-Jalil AK, Tan SL
McGill Reproductive Center, Royal Victoria Hospital, Montreal, Canada
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Fertil Steril Nov;82:

17. SLIDE 6 Standart ART Cycle

18. IVM of oocytes – laboratory procedure
Oocytes washed
24 – 48 hrs culture
Oocytes cultured in maturation medium
Mature oocyte (M-2)
Insemination
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16-18 hours
Cleavage
Insemination (ICSI)
Fertilized oocytes (2PN)
Embryos for Embryo Transfer

19. Optimal maturation media
Essential components
Optimal maturation media
Synchronized endometrium
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20. Media used for IVM Type of medium Composition Usage
SAGE - IVM media kit (ART-1600)
IVM Washing Hepes-buffered O.R., ICSI medium
IVM Oocyte Maturation Med Maturation culture
IVM Development Cleavage Embryo culture cleavage
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Medicult IVM system (Medicult no )
LAG medium Handling medium O.R.
IVM medium Maturation med. Maturation culture

21. Synchronized endometrium
Essential components
Optimal maturation media
Synchronized endometrium
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22. Endometrial Preparation Endometrial thickness on day of OPU
< 6 mm mg oestradiol
6 - 8 mm mg oestradiol
 8 mm 6mg oestradiol
Progesterone support (200mg, bid, p.v) started following ICSI
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23. SLIDE 6 Standart ART Cycle

24. SLIDE 6 Standart ART Cycle

25. A comparison of in vitro maturation and in vitro fertilization for women with polycystic ovaries
Child TJ, Philips SJ, Abdul-Jalil AK, Gulekli B, Tan SL
McGill Reproductive Center, Royal Victoria Hospital
Montreal, Canada
Obstet Gynecol 2002; 100:665-70
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26. SLIDE 6 Standart ART Cycle

27. McGill Reproductive Center, Royal Victoria Hospital
IN-VITRO MATURATION AND FERTILIZATION OF OOCYTES FROM UNSTIMULATED OVARIES: PREDICTING THE NUMBER OF IMMATURE OOCYTES RETRIEVED BY EARLY FOLLICULAR PHASE ULTRASOUND SCAN
Tan SL, Child TJ, Gülekli B
McGill Reproductive Center, Royal Victoria Hospital
Montreal, Canada
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Am J Obstet & Gynecol, 2002 ,186:684-9

28. Results No. of cycles 189 Total # of immature oocytes 1695
Viable # “ “ “
# M-II oocytes
Maturation rate (%) % # 2PN embryos
Fertilization rate (%) % Mean # immature oocytes(SD)  7.0
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Am J Obstet & Gynecol, 2002 ,186:684-9

29. SLIDE 6 Standart ART Cycle

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31. Embryology data from an IVM programme
McGill DEU
Average number of oocytes retrieved
Percentage of oocytes matured % 65.8%
Percentage of oocytes fertilized % 64.2%
Percentage of embryos cleaved % 87.5%
Average number of embryos transferred
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32. Outcomes from IVM programs
Center No of cases Clinical Preg/ET
Maria Hospital % (Korea, ’00-’02)a
Memorial Hosp %
(Taiwan)a
Hopital Antoine-B %
(France, ’02-’03)a
McGill Rep. Ctr %
(Canada, ’03)b
DEU %
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a Chian RC (2003), RBMonline 8(2):
b McGill Rep. Ctr. (2003), personal data

33. Sonuç
PCO tespit edilen kadınlardaki daha yüksek gebelik oranları bu hastalara IVF yerine rutin tedavide IVM önerilmesini düşündürmelidir
Daha önceki geleneksel IVF sikluslarına kötü cevap verenler (poor responders) ve kötü kaliteli embryolar elde edilmiş hastalarda IVM yararlı olabilir
IVM özellikle polikistik overi olan ve oosit donörü olmaya hazırlanan kadınlar için avantajları nedeni ile daha caziptir, böylelikle donör sayısını artırabilir
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34. SLIDE 6 Standart ART Cycle
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