Human Reproduction vol.5 no.8 pp.933-937, 1990
Incidence of severe ovarian hyperstimulation syndrome after GnRH agonist/HMG superovulation for in-vitro fertilization
J.Smitz1, M.Camus, P.Devroey, P.Erard, A.Wisanto and A.C.Van Steirteghem Centre for Reproductive Medicine, Academic Hospital, Vrije Universiteit Brussel, Laarbeeklaan 101, B 1090 Brussels, Belgium 'To whom correspondence should be addressed
In 1673 treatment cycles stimulated with buserelin and HMG, for IVF, GUT or ZHT, the severe ovarian hyperstimulation syndrome (OHSS) occurred in 10 cycles (0.6%). Eight patients were hyperandrogenic and showed an increased ovarian response to HMG. After replacement of a maximum of three embryos or zygotes, seven women became pregnant. Three women had a multiple gestation. All patients recovered uneventfully with conservative treatment. Support with progesterone or continuation of the agonist during the luteal phase did not prevent OHSS, confirming that the ovulatory HCG dose is the most important factor in inducing this severe complication. Luteal supplementation with HCG and/or HCG production during implantation could exacerbate OHSS. Key words: GnRH agonist/in-vitro fertilization/ovarian stimulation/polycystic ovary disease
Introduction Ovarian hyperstimulation syndrome (OHSS) in its severest form following ovulation induction therapy can be life-threatening. Whether the degree of severity of OHSS is linked to the type of therapeutic drug regimen used for ovarian stimulation remains controversial. Data in the literature indicate that this complication of superovulation can be avoided if the ovulatory HCG stimulus is withheld (Hancock et al., 1970). GnRH agonists (GnRHa) have been used routinely in combination with human menopausal gonadotrophins (HMG) for superovulation in IVF programmes since 1986. Several investigators report a higher incidence of OHSS of different grades when GnRH agonists are used (Golan et al., 1988; Caspi et al., 1989; Forman et al., 1990). In GnRHa cycles HCG luteal supplementation is frequently used and could increase the risk of OHSS. In 1673 consecutive GnRHa/HMG stimulations for IVF, gamete intra-Fallopian transfer (GIFT) or zygote intra-Fallopian transfer (ZIFT), 10 women showed severe OHSS. We analysed retrospectively the endocrine characteristics of these women before and during the treatment cycle in relation to its outcome.
© Oxford University Press
Materials and methods From June 1986 to December 1988, 1673 women were stimulated with GnRHa/HMG protocols for IVF, GIFT or ZIFT. The GnRH agonist r>Ser(TBU)6-EA10-LHRH (buserelin, Suprefact® , Hoechst AG, Frankfurt) was used. The intranasal spray of buserelin was given in a daily dose of 6 x 100 ng during waking hours. The agonist was started on day 21 of the previous cycle in ovulatory patients or after an induced progestational withdrawal bleeding in anovulatory women. We routinely used the 'desensitization' protocol (Fleming et al., 1985a) and HMG stimulation was started when the serum oestradiol (Ej) level was > (ng/1)
No follicles
No oocytes retrieved
No. oocytes, embryos or zygotes replaced
Luteal supplement
Delivery
C-sectjon 31 weeks Normal 40 weeks C-section 36 weeks Twin Normal 40 weeks Normal 39.5 weeks Normal Twin Expulsion 27 weeks Triplet
1
31
8
16
3006
15
13
3 (ZIFT)
HCG (day 4)
2
41
11
32
2493
25
17
3 (ZIFT)
HCG (day 4,6)
3 4
24 44
10 11
25 25
3077 3599
30 14
38 10
cancelled* 3 (IVF)
none HCG (day 4,8)
26
9
20
2500
10
10
3 (IVF)
Prog IM
6 7
25 28
8 11
16 34
6250 3000
17 13
14 12
1 (ZIFT) 3 (IVF)
HCG (day 4) HCG (day 4)
8
27
7
14
3435
26
24
3 (IVF)
Prog IVag
9 10
26 30
9 12
18 19
7110 2879
50 22
36 17
3 (IVF) 3 (IVF)
Prog IM Prog IVag
"We decided not to transfer embryos in this woman because of the potential nsk for hyperstimulauon. All her embryos were frozen.
Table IV. Comparison of the stimulation characteristics of OHSS cycles with normo-ovulatory women who became pregnant after treatment with the same BUS/HMG protocol
Number of days before desensiuzauon Days of HMG stimulation Number of ampoules of HMG used Preovulatory E2 concentration (ng/1) Number of oocytes retrieved
OHSS (n = 10)
Normal cycles (n = 40)
Significance
30.2 9.6 21.9 3735.0 19.1
21.0 12.3 39.2 1634.0 7.5
P P P P P
± 6.0 ± 17 ± 69 ± 1603 ±10 3
± ± ± ± ±
7.0 2.5 14.2 492 4.2
< < < <
Incidence of severe ovarian hyperstimulation syndrome after GnRH agonist/HMG superovulation for in-vitro fertilization
J.Smitz1, M.Camus, P.Devroey, P.Erard, A.Wisanto and A.C.Van Steirteghem Centre for Reproductive Medicine, Academic Hospital, Vrije Universiteit Brussel, Laarbeeklaan 101, B 1090 Brussels, Belgium 'To whom correspondence should be addressed
In 1673 treatment cycles stimulated with buserelin and HMG, for IVF, GUT or ZHT, the severe ovarian hyperstimulation syndrome (OHSS) occurred in 10 cycles (0.6%). Eight patients were hyperandrogenic and showed an increased ovarian response to HMG. After replacement of a maximum of three embryos or zygotes, seven women became pregnant. Three women had a multiple gestation. All patients recovered uneventfully with conservative treatment. Support with progesterone or continuation of the agonist during the luteal phase did not prevent OHSS, confirming that the ovulatory HCG dose is the most important factor in inducing this severe complication. Luteal supplementation with HCG and/or HCG production during implantation could exacerbate OHSS. Key words: GnRH agonist/in-vitro fertilization/ovarian stimulation/polycystic ovary disease
Introduction Ovarian hyperstimulation syndrome (OHSS) in its severest form following ovulation induction therapy can be life-threatening. Whether the degree of severity of OHSS is linked to the type of therapeutic drug regimen used for ovarian stimulation remains controversial. Data in the literature indicate that this complication of superovulation can be avoided if the ovulatory HCG stimulus is withheld (Hancock et al., 1970). GnRH agonists (GnRHa) have been used routinely in combination with human menopausal gonadotrophins (HMG) for superovulation in IVF programmes since 1986. Several investigators report a higher incidence of OHSS of different grades when GnRH agonists are used (Golan et al., 1988; Caspi et al., 1989; Forman et al., 1990). In GnRHa cycles HCG luteal supplementation is frequently used and could increase the risk of OHSS. In 1673 consecutive GnRHa/HMG stimulations for IVF, gamete intra-Fallopian transfer (GIFT) or zygote intra-Fallopian transfer (ZIFT), 10 women showed severe OHSS. We analysed retrospectively the endocrine characteristics of these women before and during the treatment cycle in relation to its outcome.
© Oxford University Press
Materials and methods From June 1986 to December 1988, 1673 women were stimulated with GnRHa/HMG protocols for IVF, GIFT or ZIFT. The GnRH agonist r>Ser(TBU)6-EA10-LHRH (buserelin, Suprefact® , Hoechst AG, Frankfurt) was used. The intranasal spray of buserelin was given in a daily dose of 6 x 100 ng during waking hours. The agonist was started on day 21 of the previous cycle in ovulatory patients or after an induced progestational withdrawal bleeding in anovulatory women. We routinely used the 'desensitization' protocol (Fleming et al., 1985a) and HMG stimulation was started when the serum oestradiol (Ej) level was > (ng/1)
No follicles
No oocytes retrieved
No. oocytes, embryos or zygotes replaced
Luteal supplement
Delivery
C-sectjon 31 weeks Normal 40 weeks C-section 36 weeks Twin Normal 40 weeks Normal 39.5 weeks Normal Twin Expulsion 27 weeks Triplet
1
31
8
16
3006
15
13
3 (ZIFT)
HCG (day 4)
2
41
11
32
2493
25
17
3 (ZIFT)
HCG (day 4,6)
3 4
24 44
10 11
25 25
3077 3599
30 14
38 10
cancelled* 3 (IVF)
none HCG (day 4,8)
26
9
20
2500
10
10
3 (IVF)
Prog IM
6 7
25 28
8 11
16 34
6250 3000
17 13
14 12
1 (ZIFT) 3 (IVF)
HCG (day 4) HCG (day 4)
8
27
7
14
3435
26
24
3 (IVF)
Prog IVag
9 10
26 30
9 12
18 19
7110 2879
50 22
36 17
3 (IVF) 3 (IVF)
Prog IM Prog IVag
"We decided not to transfer embryos in this woman because of the potential nsk for hyperstimulauon. All her embryos were frozen.
Table IV. Comparison of the stimulation characteristics of OHSS cycles with normo-ovulatory women who became pregnant after treatment with the same BUS/HMG protocol
Number of days before desensiuzauon Days of HMG stimulation Number of ampoules of HMG used Preovulatory E2 concentration (ng/1) Number of oocytes retrieved
OHSS (n = 10)
Normal cycles (n = 40)
Significance
30.2 9.6 21.9 3735.0 19.1
21.0 12.3 39.2 1634.0 7.5
P P P P P
± 6.0 ± 17 ± 69 ± 1603 ±10 3
± ± ± ± ±
7.0 2.5 14.2 492 4.2
< < < <
