IVF and Infertility Unit, Department of Obstetrics and Gynecology, Assaf-Harofeh Medical Center, Zerifin, Affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
1 To whom correspondence should be addressed. rronel{at}asaf.health.gov.il
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Key words: coasting/guidelines/IVF/ovarian hyperstimulation syndrome
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
When should coasting be employed? |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
Methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
![]() |
When to initiate and terminate coasting by administering hCG? |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Most of the clinicians publishing their experience with coasting chose to initiate the procedure at an E2 concentration of 25003000 pg/ml (Sher et al., 1995; Benavida et al., 1997
; Dhont et al., 1998
; Lee et al., 1998
; Tortoriello et al., 1998
; Fluker et al., 1999
; Al-Shawaf et al., 2001
). This relatively low threshold for coasting has proven to be effective in reducing the incidence of OHSS without compromising the cycle outcome. Higher cut-off levels (such as 6000 pg/ml) are associated with higher incidence of OHSS and the need for longer periods of coasting, leading to a lower pregnancy and implantation rate (Waldenstrom et al., 1999
).
One should remember that even after withholding exogenous gonadotrophins, there is an additional subsequent rise in serum E2 for 12 days (Sher et al., 1995; Fluker et al., 1999
; Egbase et al., 2000
) and increase in follicular diameter. When Sher et al. (1995
) initiated coasting at a plasma E2 level of >3000 pg/ml, the peak plasma concentration rose to > 6000 pg/ml during the coasting period.
Administrating hCG with an E2 level below 25003000 pg/ml, has also proven effective, placing the women at lower risk for OHSS (Sher et al., 1995; Benavida et al., 1997
; Dhont et al., 1998
; Tortoriello et al., 1998
; Al-Shawaf et al., 2001
). Dhont et al. (1998
) compared a coasting group with a control group, both having similar number of follicles (24) and maximum E2 level (3830 pg/ml). On the day of hCG administration E2 concentration was 2348 pg/ml in the coasted group and 3833 pg/ml in the control group. Only one patient developed severe OHSS in the coasted group, compared with nine patients in the control group. When an appropriate threshold for administrating hCG is determined, serum E2 should be followed and not be allowed to fall too low below it. Waldenstrom et al. (1999
) reported two cases in which hCG administration was delayed for an additional day after serum E2 had dropped below the threshold level (2724 pg/ml), leading to vaginal bleeding and cycle cancellation. In three other cases, serum E2 was allowed to fall below 272 pg/ml, resulting in the retrieval of only one to three oocytes of poor quality.
The size of the leading follicle is of importance because only follicles larger than a threshold size (diameter of >15 mm) can continue to grow for an interval without gonadotrophin support. It has been shown that after early withdrawal of gonadotrophins, when the leading follicle reached 15 mm, follicular growth continued to a size of >18 mm, with normal fertilization, cleavage and clinical pregnancy rates (Egbase et al., 2002
). Oocytes in smaller follicles may undergo maturation arrest or atresia following gonadotrophin withdrawal. If too many follicles are larger than the threshold size, cystic follicles and poor quality oocytes could result (Sher et al., 1995
). In most studies the leading follicles reached 1518 mm before initiating coasting, but optimal follicle threshold measurements is yet to be determined.
![]() |
What is the duration of coasting which is advantageous without compromising conception rate? |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Although prolonged coasting (up to 11 days) was applied with acceptable pregnancy rates, when results were analysed according to the length of coasting, a duration of more than 4 days had less favourable outcome. Because comparable fertilization and cleavage rates were found among the groups of different coasting duration, it is likely that the interval of coasting mainly affects endometrial receptivity (Ulug et al., 2002).
The duration of coasting is determined by the serum E2 level and the diameter of the leading follicles when coasting is initiated. The larger the follicles are and the higher the serum E2 is, the longer the coasting period will be before reaching the target threshold of E2 for administrating hCG. If coasting is initiated when the largest follicles are not more than 1718 mm and E2 concentration is not more than 6000 pg/ml, coasting periods of >4 days can be avoided (Waldenstrom et al., 1999; Egbase et al., 2000
).
![]() |
How successful is coasting in decreasing the incidence of OHSS? |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
![]() |
Conclusion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Coasting has proven to be an effective method to minimize the development of severe OHSS in a high-risk population. It addresses the fundamental event that leads to OHSS which is the excess of proliferation and activation of granulosa cells. Removing the FSH stimulation of granulosa cells inhibits their proliferation causing down regulation of their LH receptors, reducing the number of granulosa cells available for luteinization. It has been suggested that a sharp decline in the FSH concentration may increase the rate of granulosa cell apoptosis (Tortoriello et al., 1998). Withholding gonadotrophins will initially cause accelerated apoptosis of the granulosa cells and atresia of a large number of small follicles. It is the small follicles that are mostly responsible for the high serum E2 concentration and vasoactive compounds (Enskog et al., 1999
). The end result is reduction of chemical mediators or precursors that augment fluid extravasation. As a result of the effects described above coasting leads to reduced number of retrieved oocytes, which is in direct relationship to the duration of coasting. However, there is no significant difference in oocyte maturity, fertilizability and cleavage rate (Dhont et al., 1998
; Ulug et al., 2002
). Information about the oocyte and embryo quality in coasted patients is not available in most reports but comparable fertilization, cleavage and pregnancy rates suggest no significant impairment of quality of the oocytes obtained. A recent study showed no difference in embryo quality between embryos obtained from oocyte donors who underwent coasting and embryos obtained from donors who did not (Isaza et al., 2002
). Because candidates for coasting are high responders and have numerous follicles, many oocytes are still obtained after coasting, often leaving a large number of embryos for cryopreservation.
In this review we suggest some useful guidelines for management of high-risk patients by coasting. With appropriate use this method is effective in preventing severe OHSS and yet provides high pregnancy rates. An important decision to be made is the threshold level of E2 concentration at which coasting should be initiated. We recommend a limit of 3000 pg/ml since it leads to effective prevention of OHSS and keeps the overall duration of the coasting <4 days, which is safe and does not reduce implantation or pregnancy rates. However, coasting should not begin unless the leading follicles reach a diameter of 1518 mm. It is important to delay hCG administration until the plasma E2 concentration falls below 3000 pg/ml. Failure to do so could lead to the false impression that coasting does not prevent OHSS. A large randomized prospective trial would help to validate the effectiveness of the suggested protocol.
![]() |
FOOTNOTES |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Amso, N.N., Ahuja, K.K., Moris, N. and Shaw, R.W. (1990) The management of predicted ovarian hyperstimulation involving gonadotrophin-releasing hormone analogue with elective cryopreservation of all pre-embryos. Fertil. Steril., 53, 10871090.[ISI][Medline]
Asch, R.H., Li H.P., Balmaceda, J.P., Weckstein, L.N. and Stone, S.C. (1991) Severe ovarian hyperstimulation syndrome in assisted reproductive technology: definition of high risk groups. Hum. Reprod., 10, 13951399.
Asch, R., Ivery, G., Goldsman, M., Fredrick, J.L., Stone, S.C. and Balmaceda, J.P. (1993) The use of intravenous albumin in patients at high risk of ovarian hyperstimulation syndrome. Hum. Reprod., 8, 10151020.[Abstract]
Benavida, C.A., Davis, O., Kligman, I., Moomjy, M., Liu, H.C. and Rosenwaks, Z. (1997) Withholding gonadotrophin administration is an effective alternative for the prevention of ovarian hyperstimulation syndrome. Fertil. Steril., 67, 724727.[CrossRef][ISI][Medline]
Dhont, M., Van der Straeten, F. and De Sutter, P. (1998) Prevention of severe ovarian hyperstimulation by coasting. Fertil. Steril., 70, 847850.[CrossRef][ISI][Medline]
Egbase, P.E., Al Sharhan, M. and Grudzinskas, J.G. (1999) Early unilateral follicular aspiration compared with coasting for the prevention of severe ovarian hyperstimulation syndrome: a prospective randomized study. Hum. Reprod., 14, 14211425.
Egbase, P.E., Al Sharhan, M., Berlingieri, P. and Grudzinskas, J.G. (2000) Serum estradiol and progesterone concentrations during prolonged coasting in 15 women at risk of ovarian hyperstimulation syndrome following ovarian stimulation for assisted reproductive treatment. Hum. Reprod., 15, 20822086.
Egbase, P.E., Al Sharhan, M. and Grudzinskas, J.G. (2002). Early coasting in patients with polycystic ovarian syndrome is consistent with good clinical outcome. Hum. Reprod., 17, 12121216.
Enskog, A., Henriksson, M., Unander, M., Nilsson, L. and Brannstrom, M. (1999) Prospective study of the clinical and laboratory parameters of patients in whom ovarian hyperstimulation syndrome developed during controlled ovarian hyperstimulation for in vitro fertilization. Fertil. Steril., 71, 808814.[CrossRef][ISI][Medline]
Fluker, M.R., Hooper, W.M. and Yuzpe, A.A. (1999) Withholding gonadotrophin (coasting) to minimize the risk of ovarian hyperstimulation during superovulation and in vitro fertilization-embryo transfer cycles. Fertil. Steril., 71, 294301.[CrossRef][ISI][Medline]
Isaza, V., Garcia-Velasco, J.A., Aragones, M., Remohi, J., Simon, C. and Pellicer, A. (2002) Oocyte and embryo quality after coasting: the experience from oocyte donation. Hum. Reprod., 17, 17771782.
Lee, C., Tummon, I., Martin, J., Nisker, J., Power, S. and Tekpetey, F. (1998) Does withholding gonadotrophin administration prevent severe ovarian hyperstimulation syndrome? Hum. Reprod., 13, 11571158.[Abstract]
Rabinovici, J., Kushnir, O., Shalev, J., Goldenberg, M. and Blankstein, J. (1987) Rescue of menotrophin cycles prone to develop ovarian hyperstimulation. Br. J. Obstet. Gynaecol., 94, 10981102.[ISI][Medline]
Sher, G., Salem, R., Feinman, M., Dodge, S., Zouves, C. and Knutzen, V. (1993) Eliminating the risk of life-endangering complications following overstimulation with menotrophin fertility agents: a report on women undergoing in vitro fertilization and embryo transfer. Obstet. Gynecol., 81, 10091011.[Abstract]
Sher, G., Zouves, C., Feinman, M. and Maassarani, G. (1995) Prolonged coasting: an effective method for preventing severe ovarian hyperstimulation syndrome in patients undergoing in-vitro fertilization. Hum. Reprod., 10, 31073109.[Abstract]
Tortoriello, D.V., McGovern, P.G., Colon, J.M., Loughlin, J. and Santoro, N. (1998) "Coasting" does not adversely affect cycle outcome in a subset of highly responsive in vitro fertilization patients. Fertil. Steril., 69, 454460.[CrossRef][ISI][Medline]
Ulug, U., Bahceci, M., Erden, H.F., Shalev, E. and Ben-Shlomo, Izhar. (2002) The significance of coasting duration during ovarian stimulation for conception in assisted fertilization cycles. Hum. Reprod., 17, 310- 313.
Urman, B., Pride, S.M. and Ho Yuen, B. (1992) Management of overstimulated gonadotrphin cycles with a controlled drift period. Hum. Reprod., 7, 213217.[Abstract]
Waldenstrom, U., Kahn, J., Marsk, L. and Nilsson, S. (1999) High pregnancy rates and successful prevention of severe ovarian hyperstimulation syndrome by prolonged coasting of very hyperstimulated patients: a multicentre study. Hum. Reprod., 14, 294297.