New era of infertility treatment: Natural cycle IVF/M

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New era of infertility treatment Natural cycle
IVF/M

• Ri-Cheng Chian, MSc., Ph.D.
• Department of Obstetrics and Gynecology
• McGill University, Montreal
• Canada H3A 1A1

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Historical IVF treatment
Steptoe PC. Edwards RG. (1978) Birth after the
reimplantation of a human embryo. Lancet 312
366.
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Historical IVF treatment

• Natural cycle IVF
• Mild stimulation with clomiphene citrate or HMG
  to generate more than one oocyte
• GnRH agonists or antagonist in combination with
  gonadotropins to generate multiple oocytes

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Concerns about ovarian stimulation

• Some women are extremely sensitive to stimulation
  with exogenous gonadotropins
• At an increased risk of developing ovarian
  hyperstimulation syndrome (OHSS)
• The long-term side-effects of repeated ovarian
  stimulation may increase the risk of ovarian,
  endometrial, and breast cancers.

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Advantage of IVM for infertile patients

• To avoid side effects, including OHSS
• To simplify treatment
• Low cost

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Follicular development in the ovary
From Knight PG Glister G, ARS., 2003, 78
165-183
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Follicular growth
Stage Follicular size (mm)
Primordial 0.03 0.04 Primary
0.05 0.06 Secondary 0.07
0.11 Preantral 0.12 0.20 Early
antral 0.21 0.40 Antral
0.41 16.00 Preovulatory 16.10 20.00
Gougeon, A. (1986) Hum. Reprod., 181-87.
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Oocyte becomes fully growing size in early antral
follicle
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Oocyte maturation (from GV to M-II)
requiresapproximately 24 hours after LH surge
GV
MII
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Oocyte maturation
GV
M-I
M-II
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Updated IVM success rates

• Clinical pregnancy rate 30-35 per ET
• Implantation rate 9-15 per ET
• More than 1,000 healthy live births

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McGill IVM results by age group (own oocytes
only patients with PCO or PCOS)
Age (years) Implantation rate per embryo Clinical pregnancy rate per cycle started Live birth rate per cycle started
lt35 14.4 34.8 20.0
35-37 5.4 20.0 20.0
38-40 5.0 20.0 10.0
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Previous IVM protocol for women with PCO or PCOS

• On day 8 to exclude the development of a dominant
  follicle
• The size of all follicles on day 8 has to be lt10
  mm in diameter
• Schedule for hCG injection 36 h prior to egg
  collection

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Why exclude the development of a dominant
follicle and the size of all follicles on day 8
has to be lt10 mm in diameter?

• It is a common belief that the development of
• a dominant follicle suppresses the remaining
• small follicles and induces atresia of these
• small follicles.

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Bovine ovaries
Early phase
Late phase
a
b
a
c
Luteal phase
 
 
 
 
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(Chian et al., RBMOnline, 2002 4127-132.)
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(Chian et al., RBMOnline, 2002 4127-132.)
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(Chian et al., RBMOnline, 2002 4127-132.)
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(Chian et al., RBMOnline, 2002 4127-132.)
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The results from this experiment indicate

• The maturational and developmental competence of
  immature oocytes derived from the small antral
  follicles is not affected by the presence of a
  dominant follicle and phases of folliculogenesis.

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IVM protocol for women with PCO or PCOS

• On day 8 to exclude the development of a dominant
  follicle
• The size of all follicles on day 8 has to be lt10
  mm in diameter
• Schedule for hCG injection 36 h prior to egg
  collection

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Case report
Age 41 Dominant follicle (gt16 mm)
0 No. of eggs retrieved (lt8 mm)
2 No. of eggs matured at 48 h () 2
(100) No. of eggs fertilized () 2
(100) No. of eggs cleaved () 1
(50) No. of embryos transferred
1 Pregnancy Live-birth
Healthy baby boy
Chian et al. (Fertil Steril 2004 821675-8.)
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Case report (cont.)
Age 39 No. of eggs retrieved
10 M-II 2 M-I 2 GV 6 No. of
eggs matured () 6 (60) 0
h 2 6 h 2 48 h 2 No. of eggs
fertilized () 6 (100) No. of eggs
cleaved () 6 (100) No. of embryos
transferred 3 Live birth
Healthy baby girl
Chian et al. (Fertil Steril 2004 821675-8.)
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Case report (cont.)
Age 32 No. of eggs retrieved
17 M-II 5 GV 12 No.
of eggs matured () 15
(88.2) 0 h 5 24 h 7 48 h 3 No. of
eggs fertilized () 10 (66.7) No. of
eggs cleaved () 10 (100) No. of
embryos transferred 4 Live
birth Healthy baby boy
Chian et al. (Fertil Steril 2004 821675-8.)
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From these results confirmed

• Developmental competence of immature human
  oocytes retrieved from the small antral follicles
  is not affected by the presence of a dominant
  follicle during menstrual cycle.

Chian et al. (Fertil Steril 2004 821675-8.)
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IVF/IVM protocol

• Women with normal ovaries
• gt 7 antral follicles seen under baseline
  ultrasound scan and FSH level under 10 mIU/ml
• The leading follicle reached to 12-14 mm in
  diameter and endometrium thickness reached to at
  least 6.0 mm, hCG (10,000 IU) is given
• Egg retrieval is scheduled 36 hrs later

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Mature and immature oocytes retrieved from
natural cycle IVF combined with IVM treatment
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Interpretation
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Patient selection
Baseline USG on MCD 35
lt 7
Follicle number
Irr. mens
Reg. mens
Nat. IVF with IVM
COH
IVM
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The percentages of completed treatment cycles
distributed by natural cycle IVF/M, IVM or COH.
Total of 378 patients started 417 treatment
cycles .
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The percentages of completed treatment cycles
based on age groups distributed by natural cycle
IVF/M, IVM or COH.
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Comparison of clinical outcome in patients
distributed into IVF/M, IVM or COH treatment
IVF/M IVM COH
No. of cycles started (patients) 153 (140) 63 (56) 201 (182)
No. of cycles completed (patients) 151 (138) 63 (56) 196 (177)
Age (MeanSD) 31.43.7 31.44.0 34.44.8
No. of oocytes retrieved (MeanSD) 1,826 (12.15.6) 1,017 (16.110.3) 2,079 (10.66.6)
No. of oocytes matured () 1,216 (66.6) 658 (64.7) 1,875 (90.2)
No. of oocytes fertilized () 996 (81.9) 519 (78.9) 1,485 (79.2)
No. of zygotes cleaved () 928 (93.2) 469 (90.4) 1,429 (96.2)
No. of embryos transferred (MeanSD) 462 (3.10.8) 210 (3.30.6) 513 (2.50.4)
No. of clinical pregnancies obtained () 61 (40.4) 26 (41.3) 74 (37.8)
No. of embryos implanted () 82 (17.8) 35 (16.7) 103 (20.1)
No. of live births () Singleton Twin 21 (34.4) 18 3 8 (30.8) 7 1 35 (47.3) 21 14
No. of ongoing pregnancies 23 (37.7) 8 (30.8) 21 (28.4)
No. of miscarriages () 17 (27.9) 10 (38.5) 18 (24.3)
Significantly different compared with other two
groups (Plt0.05).
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Conclusions
Natural cycle IVF/M is an efficient treatment
for women with Infertility, especially for women
under 35 yrs of age.
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Acknowledgments

• Staff of McGill Reproductive Center
• Dr. Lim, J-H., from Maria Infertility Hospital,
  Seoul, Korea

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E-mail ri-cheng.chian_at_muhc.mcgill.ca