Departments of Infertility and Maternal-Fetal Medicine, Instituto Valenciano de Infertilidad (IVI), Plaza de la Policía Local, 3, 46015, Valencia, Spain
1 To whom correspondence should be addressed. e-mail: apellicer{at}ivi.es
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Abstract |
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Keywords: conservative management/literature review/oophorectomy/ovarian hyperstimulation syndrome/surgery
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Introduction |
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The self-limiting course of the disease is well known (Whelan and Vlahos, 2000), especially when pregnancy is not achieved. The severe form of OHSS, present in about 0.25% of cases (Navot et al., 1992
; Al-Ramahi, 1999
; Forman, 1999
; Graf and Fischer, 1999
), includes many serious manifestations, both clinical and biochemical (Balasch et al., 1998
; Al-Ramahi, 1999
; Murdoch and Evbuomwan, 1999
; Whelan and Vlahos, 2000
). A multiple organ failure is expected in some patients, and a few cases of death have been reported (Cluroe and Synek, 1995
; Semba et al., 2000
). The estimated mortality associated with OHSS has been calculated as 1/450 000500 000 (Brinsden et al., 1995
).
The best treatment in OHSS is really prevention (Navot et al., 1992). Several risk factors for this disease, some of them debatable, have been described before and during COH, as shown in Table I. Preventive measures should be taken as soon as these factors are identified. Many approaches have been reported to date (Table II). The success rates of these preventive protocols have varied, some of them proven to be effective not only for avoiding OHSS but also for reducing its severity.
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Management of OHSS |
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Alternative approaches have been proposed. Re-infusion or autotransfusion of ascitic fluid, similar to that applied in cirrhotic patients, has shown limited but promising results (Fukaya et al., 1994; Koike et al., 2000
; Takamizawa et al., 2002
). In other cases of severe OHSS, aspiration of the corpus lutea (Fakih and Bello, 1992
; Oleszczuk et al., 2002
) and even termination of pregnancy (Reed et al., 1990
; Whelan and Vlahos, 2000
) have halted the disease.
As cited above, all the therapies for OHSS described in the literature are conservative. We should bear in mind that most women who undergo COH are infertile and, therefore, the possibility of their becoming pregnant must always be the foremost aim. This is especially crucial in cases of oocyte donors whose fertility potential can be adversely affected after an aggressive treatment when OHSS occurs. Of the many cases of severe OHSS encountered every year in fertility clinics, only a very few cases of death have been reported (Cluroe and Synek, 1995; Semba et al., 2000
). To date, no author has ever proposed an irreversible surgical solution for the treatment of this syndrome. Therefore, we do not believe that oophorectomy (total or partial) is an option in severe OHSS, as suggested by Amarin (2003
), except for cases of irreversible ovarian damage after adnexal torsion (Pryor et al., 1995
; Sills et al., 2000
).
For many years, it has been shown that any surgical procedure resulting in loss of viable ovarian cortex could reduce the ovarian reserve, leading to a decreased response to gonadotrophins and to a shortening of the life span of the ovarian tissue (Donnez et al., 1996; Chang et al., 1998
; Hemmings et al., 1998
; Saleh and Tulandi, 1999
). It is also known that women with only one ovary show reduced ovarian reserve due to the depletion of the total number of primordial follicles and may have a shorter reproductive life span (Lass, 1999
). Moreover, surgical techniques in reproduction such as ovarian wedge resection, carried out in PCOS women, were abandoned because of the risk of post-surgical adhesion formation (Farquhar et al., 2001
). Among the different surgical treatments described in gynaecology, oophorectomy is one of the most aggressive. Surgeons prefer to avoid it in benign pathologies. It is important not to confuse mutilating surgery with procedures developed for improving the ovarian response. Laparoscopic drilling of ovaries in PCOS women was designed to improve the follicular response and to reduce the risk of OHSS after COH (Rimington et al., 1997
). Although its effectiveness as a primary treatment for subfertile patients with anovulation and PCOS is undetermined and does not seem to influence pregnancy or miscarriage rates following COH, this therapy does seem to reduce the risk of OHSS and has not been correlated with a later decreased fertility (Rimington et al., 1997
; Farquhar et al., 2001
; Amer et al., 2002
). Hence, against what Amarin (2003
) suggested, the long-term anatomical and physiological sequelae do not seem to be similar in ovarian drilling and partial oophorectomy.
Partial or total oophorectomy should only be an option in severe OHSS if other therapies could not demonstrate good results. However, there are many effective conservative approaches employed in the battle against this syndrome. Even in cases of adnexal torsion, laparoscopic or laparotomic unwinding is the treatment of choice when the ovary remains viable and functional (Gorkemli et al., 2002), also in advanced gestation (Levy et al., 1995
). An infertile woman or oocyte donor usually prefers to spend even some days in the intensive care unit of a hospital rather than have her fertility potential and ovary function adversely affected, or undergo a risky surgery such as partial oophorectomy in a hyperstimulated ovary. In addition, owing to the lack of experience, partial oophorectomy cannot be offered to the patient as a proven solution for severe OHSS. From a medical point of view, termination of pregnancy would be a better option in very severe late OHSS, as patients with this syndrome tend to be good responders and are likely to become pregnant again in a future cycle.
Our experience is in accordance with previous reports. We have collected all those cases of severe OHSS that occurred in our clinic in the last 2 years, thereby including the more recently described conservative strategies. From the beginning of January 2000 to the end of October 2002, 13 736 IVF cycles were carried out in the five Spanish clinics of the Instituto Valenciano de Infertilidad (Valencia, Madrid, Murcia, Sevilla, Almería). Only 144 cases of severe OHSS occurred, implying an incidence of 1.05%. The criteria used to classify OHSS as severe were the following: tense or painful ascites, difficulty in breathing, hydrothorax, pericardial effusion, oligouria, adnexal torsion, renal failure, hepatic damage, thrombo-embolic events, adult respiratory distress syndrome, haematocrit ≥45% or increased more than 30% over a previous one, ≥15 000 leukocytes/mm3, electrolyte imbalance (sodium <135 mEq/l and/or potassium >5 mEq/l), creatinine >1.0 g/dl, coagulation abnormalities or any serious organic complication. We tend towards an early active management in cases of moderate and severe OHSS on an outpatient basis, carrying out mainly isolated or repeated transvaginal paracentesis, oral and/or intravenous fluid balance, albumin infusion and close follow up. Hyperstimulated women at risk of thrombosis are put on a low molecular weight heparin regimen. Only when clinical or laboratory parameters are severely affected or when the patients condition fails to improve is hospitalization mandatory. The vast majority of our severe OHSS cases presented tense or abundant ascites, difficulty in breathing, oliguria and increased white or red blood cell counts; maybe due to early active therapy and close monitoring, only few of these presented truly life-threatening conditions. We performed aspiration of the corpus lutea in three women with twin pregnancies and OHSS not responding to medical management. One of these also underwent a laparoscopy in order to untwist an adnexal torsion at 7 weeks gestation, and another presented hydrothorax and sacral oedema. They showed a sudden recovery within 24 hours and there was no need for further conservative treatment. No case of death was registered and it was not necessary to perform mutilating ovarian surgery. Table III shows a summary of the management of our severely hyperstimulated patients.
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Acknowledgements |
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References |
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Aboulghar, M.A., Mansour, R.T., Serour, G.I., Sattar, M.A., Amin, Y.M. and Elattar, I. (1993) Management of severe ovarian hyperstimulation syndrome by ascitic fluid aspiration and intensive intravenous fluid therapy. Obstet. Gynecol., 81, 108111.[Abstract]
Aboulghar, M.A., Evers, J.H. and Al-Inany, H. (2000) Intra-venous albumin for preventing severe ovarian hyperstimulation syndrome. Cochrane Database Syst. Rev., 2, CD001302.
Albert, C., Garrido, N., Mercader, A., Rao, C.V., Remohí, J., Simón, C. and Pellicer, A. (2002) The role of endothelial cells in the pathogenesis of ovarian hyperstimulation syndrome. Mol. Hum. Reprod., 8, 409418.
Al-Ramahi, M. (1999) Severe OHSS: Decreasing the risk of severe ovarian hyperstimulation syndrome. Hum. Reprod., 14, 24212422.
Amarin, Z.O. (2003) Bilateral partial oophorectomy in the management of severe ovary hyperstimulation syndrome. An aggressive, but perhaps life-saving procedure. Hum. Reprod., 18, 16.[CrossRef][ISI][Medline]
Amer, S.A.K.S., Banu, C., Li, T.C. and Cooke, I.D. (2002) Long-term follow-up of patients with polycystic ovary syndrome after laparoscopic ovarian drilling: endocrine and ultrasonographic outcomes. Hum. Reprod., 17, 28512857.
Asch, R.H., Ivey, G., Goldsman, M., Frederick, J.L., Stone, S.C. and Balmaceda, J.P. (1993) The use of intravenous albumin in patients at high risk of severe ovarian hyperstimulation syndrome. Hum. Reprod., 8, 10151020.[Abstract]
Balasch, J., Fabregues, F., Arroyo, V., Jiménez, W., Creus, M. and Vanrell, J.A. (1996) Treatment of severe ovarian hyperstimulation syndrome by a conservative medical approach. Acta Obstet. Gynecol. Scand., 75, 662667.[ISI][Medline]
Balasch, J., Fabregues, F. and Arroyo, V. (1998) Peripheral arterial vasodilatation hypothesis: a new insight into the pathogenesis of ovarian hyperstimulation syndrome. Hum. Reprod., 13, 27182730.
Bellver, J., Navarro, J. and Remohí, J. (2000) Estrategias para la reducción del riesgo del síndrome de hiperestimulación ovárica. Folia Clínica en Obstetricia y Ginecología, 24, 5259.
Blankstein, J., Shalev, J., Saadon, T., Kukia, E.E., Rabinovici, J., Pariente, C., Lunenfeld, B., Serr, D.M. and Mashiach, S. (1987) Ovarian hyperstimulation syndrome: prediction by number and size of preovulatory ovarian follicles. Fertil. Steril., 47, 597602.[ISI][Medline]
Brinsden, P.R., Wada, I., Tan, S.L., Balen, A. and Jacobs, H.S. (1995) Diagnosis, prevention and management of ovarian hyperstimulation syndrome. Br. J. Obstet. Gynaecol., 10, 767772.
Buyalos, R.P. and Lee, C.T. (1996) Polycystic ovary syndrome: pathophysiology and outcome with in vitro fertilization. Fertil. Steril., 65, 110.[ISI][Medline]
Caspi, E., Ron-El, R., Golan, A., Nachum, H., Herman, A., Soffer, Y. and Weinraub, Z. (1989) Results of in vitro fertilization and embryo transfer by combined long-acting gonadotropin-releasing hormone analog D-Trp-6-luteinizing hormone-releasing hormone and gonadotropins. Fertil. Steril., 51, 9599.[ISI][Medline]
Chang, M.Y., Chiang, C.H., Hou, H.C. et al. (1998) The outcome of assisted reproductive therapies in patients with endometriosis is affected by antral follicle count and previous endometrioma surgeries. Proceedings of the Sixth World Congress on Endometriosis; 1998 June 30 July 4; Quebec City, Quebec, Canada, Abstract, p180.
Cluroe, A.D. and Synek, B.J. (1995) A fatal case of ovarian hyperstimulation syndrome with cerebral infarctation. Pathology, 27, 344346.[ISI][Medline]
Donnez, J., Nisolle, M., Gillet, N., Smets, M., Bassil, S. and Casanas-Roux, F. (1996) Large ovarian endometriomas. Hum. Reprod., 11, 641646.[Abstract]
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 Brännström, 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]
Fakih, H. and Bello, S. (1992) Ovarian cyst aspiration: a therapeutic approach to ovarian hyperstimulation syndrome. Fertil. Steril., 58, 829832.[ISI][Medline]
Farquhar, C., Vandekerckhove, P. and Lilford, R. (2001) Laparosocopic drilling by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome. Cochrane Database Syst. Rev., 4, CD001122.
Fluker, M.R., Copeland, J.E. and Yuzpe, A. (2000) An ounce of prevention: outpatient management of the ovarian hyperstimulation syndrome. Fertil. Steril., 73, 821824.[CrossRef][ISI][Medline]
Forman, R.G. (1999) Severe OHSS- an acceptable price? Hum. Reprod., 14, 26872688.
Fukaya, T., Chida, S., Terada, Y., Funayama, Y. and Yajima, A. (1994) Treatment of severe ovarian hyperstimulation syndrome by ultrafiltration and reinfusion of ascitic fluid. Fertil. Steril., 61, 561564.[ISI][Medline]
García-Velasco, J.A., Simón, C., Valbuena, D., Peinado, J.A., Remohí, J. and Pellicer, A. (2000) Nuevas estrategias para la prevención del síndrome de hiperestimulación ovárica. El caso de las pacientes con alta respuesta en estimulación ovárica para FIV. Ponencia Symposium Serono, XXIII Congreso Nacional de la Sociedad Española de Fertilidad. Sevilla.
Gómez, R., Simón, C., Remohí, J. and Pellicer, A. (2002) Vascular endothelial growth factor receptor-2 activation induces vascular permeability in hyperstimulated rats and this effect is prevented by receptor blockade. Endocrinology, 143, 43394348.
Gorkemli, H., Camus, M. and Clasen, K. (2002) Adnexal torsion after gonadotrophin ovulation induction for IVF or ICSI and its conservative treatment. Arch. Gynecol. Obstet., 267, 46.
Graf, M.A. and Fischer, R. (1999) Severe OHSS. An epidemic of severe OHSS: a price we have to pay? Hum. Reprod., 14, 29302931.
Haning, A.J., Austin, C., Carlson, I., Kuzama, D. and Zweibel, W. (1983) Plasma estradiol is superior to ultrasound and urinary estradiol glucuronide as a predictor of ovarian hyperstimulation during induction of ovulation with menotropins. Fertil. Steril., 40, 3136.[ISI][Medline]
Hemmings, R., Bissonette, F. and Bouzayen, R. (1998) Results of laparoscopic treatments of ovarian endometriomas: laparosocopic ovarian fenestration and coagulation. Fertil. Steril., 70, 527529.[CrossRef][ISI][Medline]
Koike, T., Araki, S., Minakami, H., Ogawa, S., Sayama, M., Shibahara, H. and Sato, I. (2000) Clinical efficacy of peritoneovenous shunting for the treatment of severe ovarian hyperstimulation syndrome. Hum. Reprod., 15, 113117.
Lainas, T., Petsas, G., Stavropoulou, G., Alexopoulou, E., Iliadis, G. and Minaretzis, D. (2002) Administration of methylprednisolone to prevent severe ovarian hyperstimulation syndrome in patients undergoing in vitro fertilization. Fertil. Steril., 78, 529533.[CrossRef][ISI][Medline]
Lass, A. (1999) The fertility potential of women with a single ovary. Hum. Reprod. Update, 5, 546550.
Levy, T., Dicker, D., Shalev, J., Dekel, A., Farhi, J., Peleg, D. and Ben-Rafael, Z. (1995) Laparoscopic unwinding of hyperstimulated ischaemic ovaries during the second trimester of pregnancy. Hum. Reprod., 10, 14781480.[Abstract]
Ludwig, M., Felberbaum, R.E., Devroey, P., Albano, C., Riethmuller-Winzen, H., Schuler, A., Engel, W. and Diedrich, K. (2000) Significant reduction of the incidence of ovarian hyperstimulation syndrome (OHSS) by using the LHRH antagonist Cetrorelix (Cetrotide) in controlled ovarian stimulation for assisted reproduction. Arch. Gynecol. Obstet., 264, 2932.
Lyons, C.A., Wheeler, C.A., Frishman, G.N., Hackett, R.J., Seifer, D.B. and Haning, R.V. Jr (1994) Early and late presentation of the ovarian hyperstimulation syndrome: two distinct entities with different risk factors. Hum. Reprod., 9, 792799.[Abstract]
Mathur, R.S., Akande, A.V., Keay, S.D., Hunt, L.P. and Jenkins, J.M. (2000) Distinction between early and late ovarian hyperstimulation syndrome. Fertil. Steril., 73, 901907.[CrossRef][ISI][Medline]
Murdoch, A.P. and Evbuomwan, I. (1999) Severe complications of ovarian hyperstimulation syndrome are preventable. Hum. Reprod., 14, 29222923.
Navot, D., Relou, A., Birkenfeld, A., Rabinowitz, R., Brzezinski, A. and Margalioth, E. (1988) Risk factors and prognostic variables in the ovarian hyperstimulation syndrome. Am. J. Obstet. Gynecol., 159, 210215.[ISI][Medline]
Navot, D., Bergh, P.A. and Laufer, N. (1992) Ovarian hyperstimulation syndrome in novel reproductive technologies: prevention and treatment. Fertil. Steril., 58, 249261.[ISI][Medline]
Oleszczuk, J., Leszczynska-Gorzelak, B., Kaminski, K. and Baranowski, W. (2002) Evaluation of ovarian cysts by means of transabdominal fine needle aspiration or laparotomy in pregnant women. Ginekol. Pol., 73, 36770.[Medline]
Olivennes, F. and Frydman, R. (1998) Friendly IVF: the way of the future? Hum. Reprod., 13, 11211124.
Olivennes, F., Cunha-Filho, J.S., Fanchin, R., Bouchard, P. and Frydman, R. (2002) The use of GnRH antagonists in ovarian stimulation. Hum. Reprod. Update, 8, 279290.
Padilla, S.L., Zamaria, S., Baramki, T.A. and García, J.E. (1990) Abdominal paracentesis for ovarian hyperstimulation syndrome with severe pulmonary compromise. Fertil. Steril., 53, 365367.[ISI][Medline]
Pelinck, M.J., Hoek, A., Simons, A.H. and Heineman, M.J. (2002) Efficacy of natural cycle IVF: a review of the literature. Hum. Reprod. Update, 8, 129139.
Pryor, R.A., Wiczyk, H.P. and OShea, D.L.(1995) Adnexal infarctation after conservative surgical management of torsion of a hyperstimulated ovary. Fertil. Steril., 63, 13441346.[ISI][Medline]
Reed, A.P., Tausk, H. and Reynolds, H. (1990) Anesthetic considerations for severe ovarian hyperstimulation syndrome. Anesthesiology, 73, 12751277.[ISI][Medline]
Rimington, M.R., Walker, S.M. and Shaw, R.W. (1997) The use of laparoscopic ovarian electrocautery in preventing cancellation of in-vitro fertilization treatment cycles due to risk of ovarian hyperstimulation syndrome in women with polycystic ovaries. Hum. Reprod., 12, 14431447.[Abstract]
Rimington, M.R., Simona, E.G. and Ahuja, K.K. (1999) Counselling patients undergoing controlled ovarian stimulation about the risks of ovarian hyperstimulation syndrome. Hum. Reprod., 14, 29212922.
Saleh, A. and Tulandi, T. (1999) Reoperation after laparoscopic treatment of ovarian endometriomas by escisión and by fenestration. Fertil. Steril., 72, 322324.[CrossRef][ISI][Medline]
Semba, S., Moriya, T., Youssef, E.M. and Sasano, H. (2000) An autopsy case of ovarian hyperstimulation syndrome with massive pulmonary edema and pleural effusion. Pathol. Int., 50, 549542.[CrossRef][ISI][Medline]
Shaker, A.G., Zosmer, A., Dean, N., Bekir, J.S., Jacobs, H.S. and Tan, S.L. (1996) Comparison of intravenous albumin and transfer of fresh embryos with cryopreservation of all embryos for subsequent transfer in prevention of ovarian hyperstimulation syndrome. Fertil. Steril., 65, 992996.[ISI][Medline]
Shalev, E., Giladi, Y., Matilsky, M. and Ben-Ami, M. (1995) Decreased incidence of ovarian hyperstimulation syndrome in high risk in-vitro fertilization patients receiving intravenous albumin: a prospective study. Hum. Reprod., 10, 13731376.[Abstract]
Sher, G., Zouves, C., Feinman, M. And Maassarani, G. (1995) Prolonged coasting: and effective method for preventing severe ovarian hyperstimulation syndrome in patients undergoing in-vitro fertilization. Hum. Reprod., 10, 31073109.[Abstract]
Sills, E.S., Poynor, E.A. and Moomjy, M. (2000) Ovarian hyperstimulation and oophorectomy following accidental daily clomiphene citrate use over three consecutive months. Reprod. Toxicol., 14, 541543.[CrossRef][ISI][Medline]
Takamizawa, S., Shibahara, H., Taneichi, A., Obara, H., Fujiwara, H., Ogawa,S., Koike, T., Idei, S. and Sato, I. (2002) Dynamic changes of the immunoglobulins in patients with severe ovarian hyperstimulation syndrome: efficacy of a novel treatment using peritoneo-venous shunt. Am. J. Reprod. Immnunol., 47, 2530.[CrossRef]
Tiitinen, A., Husa, L.M., Tulppala, M., Simberg, M. and Seppala, M. (1995) The effect of cryopreservation in prevention of ovarian hyperstimulation syndrome. Br. J. Obstet. Gynaecol., 102, 326329.[ISI][Medline]
Tomazevic, T. and Meden-Vrtovec, H. (1996) Early timed follicular aspiration prevents severe ovarian hyperstimulation syndrome. J. Assist. Reprod. Genet., 13, 282286.[ISI][Medline]
Trounson, A., Wood, C. and Kausche, A.(1994) In vitro maturation and the fertilization and development competence of oocytes recovered from untreated polycystic ovarian patients. Fertil. Steril., 62, 353362.[ISI][Medline]
Whelan, J.G. III and Vlahos, N.F. (2000) The ovarian hyperstimulation syndrome. Fertil. Steril., 73, 883896.[CrossRef][ISI][Medline]