FERTILITY AND STERILITY
Vol. 58, No.4, October 1992
Copyright" 1992 The American Fertility Society
Printed on ocw·tree paper in U.S.A.
Ovarian cyst aspiration: a therapeutic approach to ovarian hyperstimulation syndrome
Hasan Fakih, M.D.*t Sandra Bello, B.S.:\: Michigan State University, East Lansing, and Saginaw Cooperative Hospitals, Inc., Saginaw, Michigan
Ovarian hyperstimulation is an iatrogenic complication of multiple follicular stimulation with menotropic medications before in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT) procedures. Severity of the syndrome can range from mild to severe with symptoms of ovarian enlargement, ascites, pleural effusion, and complications of hemoconcentration, hypercoagulability, and hypovolemia. These complications can be potentially lifethreatening. The pathophysiology of this syndrome is unclear, and medical management has traditionally been conservative and supportive consisting of bedrest, replacement of fluids, and volume expanders. Abdominal paracentesis has been introduced as a means to improve the symptoms of ascites and probably shorten the duration of the illness (1). Pregnancy outcome is usually poor with >50% resulting in spontaneous miscarriages (2). We are reporting a new approach for the treatment of ovarian hyperstimulation syndrome (OHSS). Transvaginal ultrasound (US)-guided aspiration of ovarian cysts and ascitic fluid was performed in seven women with OHSS with good outcome. MATERIALS AND METHODS
The diagnosis of severe OHSS was made when the patients presented after GIFT or IVF with pelvic discomfort, and pelvic US documented the presence Received December 9, 1991; revised and accepted May 27, 1992.
* Department of Obstetrics and Gynecology, Michigan State University. t Reprint requests: Hasan Fakih, M.D., Department of Reproductive Endocrinology and Infertility, Saginaw Cooperative Hospitals, Inc., 1000 Houghton Avenue, Saginaw, Michigan 48602. :t: Michigan State University medical student. Vol. 58, No.4, October 1992
of ascites and enlarged cystic ovaries with an ovarian diameter > 12 cm. Additional symptoms included shortness of breath and, in some, decreased urine output. All patients had a positive pregnancy test. Seven were treated with transvaginal aspiration of ovarian cysts and of ascitic fluid. The aspiration was performed in the operating room under sterile conditions. Before aspiration, 500 cc of a plasma expander was infused over 1 hour (Table 1). An additional 500 to 1,000 mL were then infused during the procedure. The patient was then placed in an antiTrendelenberg position to facilitate pooling of ascitic fluid in the pelvis. The aspirating needle was introduced transvaginally into the cul-de-sac under direct US guidance, and the ascitic fluid was aspirated. The needle was directed into the ovarian cysts, and these were aspirated sequentially. All accessible cysts, regardless of size, were aspirated from both ovaries. The patient was given 50 to 100 mg of progesterone (P) in oil intramuscularly (1M) and was monitored for 1 hour in the recovery room. If stable, she was transferred to the outpatient department for 2 more hours of observation and was discharged home upon documentation of stable vital signs, with normal serum electrolytes, kidney function tests, and coagulation profile. The patients were maintained on P supplementation for 2 more weeks. They were monitored weekly for serum estradiol, P, and human chorionic gonadotropin (heG) levels along with pelvic US assessment of the pregnancy and of ovarian size. The patients were instructed to contact us upon development of pelvic discomfort or vaginal bleeding. RESULTS
Since May 1987, eight women were diagnosed with severe OHSS among 800 procedures for an incidence Fakih and Bello Communications-in-brief
829
Table 1
Clinical Data of Women With Severe OHSS Treated by Transvaginal Ovarian Cyst Aspiration
Case no.
Amounts of fluid aspirated
1
a.2,000 b.2,000 c.2,100 a.2,000 a. 500 a. 500 a.l,400 b.l,500 c.l,700 a.l,500 a.3,000
Plasma expander
Luteal support postaspiration
Length of hospital stay
a. None b. None c. P 50:1: a. P 100:1: a. None b. P 100:1: a. P 50:1:
a. 7§ b. 7§ c. Outpatient Outpatient Outpatient Outpatient Outpatient
Single term delivery Miscarried Twin term delivery Twin term delivery
b. P 50:1: c. P 50:1: a. P 50:1:
Outpatient Outpatient Outpatient
Twin preterm delivery Twin progressing pregnancy
Outcome
mL
2 3 4 5 6 7
a. None b. Plasmanate-l,500* c. Plasmanate-l,500* a. Rheomacrodex-2,000* a. None b. Plasmanate-500* a. Plasmante-l,OOO* b. Plasmante-l,OOO* c. Albumin-25 gt a. Dextran 40-500* a. Dextran 40-1,000*
* Gram. t Milliliter.
:1: Milligram 1M. § Days.
of 1 %. The first patient was treated symptomatically, and the pregnancy ended in a spontaneous miscarriage at 8 weeks of gestation. Ovarian cysts formed as part of the complex of severe ORSS in our patient population were noted to be ultrasonographically clear. This finding indicated that these are follicular rather than luteal in origin. Moreover, most of the presenting symptoms in women with severe ORSS are known to be related to ovarian enlargement. The above findings prompted us to proceed with aspiration of ovarian cysts in all subsequent patients with the diagnosis of severe ORSS. The first transvaginal aspiration of ovarian cysts for the treatment of severe ORSS was performed in September 1988. The patient related immediate relief of symptoms without any complications and thereafter had a normally progressing pregnancy. In this first patient, the smaller ovarian cysts were intentionally avoided during the aspiration procedure. She later required two additional aspiration procedures 1 week apart because of recurrence of symptoms and the findings of ovarian enlargement by pelvic US. In subsequent patients, however, all accessible ovarian cysts, regardless of size, were aspirated, and only one of six patients required additional aspiration. All subsequent procedures were performed on an outpatient basis. None of the patients developed any complications related to the procedure in the immediate postoperative period or later on during the pregnancy. The average age of the patients was 25.2 years. All women had laparoscopic egg retrieval. The presenting symptoms included abdominal distention, bloating, and pelvic pain along with a positive pregnancy test. Three women complained of shortness 830
Fakih and Bello
Single term delivery
Communications-in-brief
of breath. On pelvic US scanning, they all had enlarged ovaries, 12 cm or greater in diameter, along with ascitic fluid in the pelvic cavity. Cases 1, 5, 6, and 7 had concomitant hemoconcentration (hematocrit > 42). Patients 1 and 4 had elevated liver enzyme levels. Serum sodium levels were low or low normal in all patients. Platelet counts were elevated (>500,000) in cases 5 and 7, respectively. None of the patients had abnormal coagulation profiles. Table 1 summarizes the treatment instituted and outcome in these patients. An average of 1,700 cc of fluid was aspirated per patient. Marked improvement in all patient's symptoms immediately after aspiration of fluid was observed. All patients had normal serum electrolytes, kidney function tests, and coagulation profiles before discharge. Abnormal liver functions persisted for an additional 2 to 4 weeks. Patients were followed by weekly US assessments of ovarian size, ascitic fluid volume, and fetal viability. Five of seven patients had normal ovarian size on follow-up with minimal ascitic fluid. All five women had persistent relief of pelvic discomfort and dyspnea. The remaining two patients were readmitted for aspiration because of accumulation of ascitic fluid and recurrence of symptoms. Except for our first ovarian aspiration case, the rest of the patients were treated on an outpatient basis. All patients received P suppositories for luteal support. Among the seven cases in whom ovarian cyst aspiration was performed, all, except case number 3, received P 1M after aspiration. Incidentally, this pregnancy ended with a spontaneous miscarriage, although good fetal heart activity could be seen until 4 weeks after aspiration. As can be seen in Table 1, Fertility and Sterility
all pregnancies except one carried beyond 20 weeks' gestation. DISCUSSION
Ovarian hyperstimulation syndrome is a wellknown side effect of controlled ovulation induction. With the introduction of IVF and related technologies, the number of women hyperstimulated with menotropins is increasing substantially all over the world, and this has resulted in an increased incidence of this syndrome (2). The syndrome in its severe form is reported to occur in 0.008% to 10% of stimulated cycles. Severe ORSS usually occurs in conceptual cycles, and >50% of these will end in a spontaneous miscarriage (2). Severe ORSS is a life-threatening condition, and patients will need hospitalization because the condition may rapidly deteriorate. The abdomen is usually very distended and tense with the ovaries larger than 12 cm in diameter. An acute fluid shift of the intravascular space may result in ascites, hydrothorax, and generalized edema. This fluid shift is caused by an increase of the capillary permeability, allowing fluid escape into the third space leading to ascites, pleural effusion, hypovolemia, and hemoconcentration with electrolyte imbalance. This may progress rapidly to hypovolemic shock, oliguria, and even coagulation disorders and thromboembolic phenomena. In a few cases, thromboembolic incidences were reported resulting in death (2). It is believed that this fluid shift is mediated by a vasoactive substance secreted by the ovaries. Estrogen, prostaglandins, histamine, and prorenin have been proposed as possible mediators (3-5). Aspiration of the ovarian cysts in women with severe ORSS may reduce the ovarian production of these hormones, thus reducing the stimulus propagating the disease process. Ovarian hyperstimulation syndrome is known to occur in spite of aspiration of ovarian follicles for the purpose of IVF or the GIFT procedure. In our experience of 800 consecutive controlled ovarian hyperstimulation cycles for the purpose of assisted reproductive technologies, eight patients fulfilled the criteria of severe ORSS. This complication in our series has occurred only in women with a positive pregnancy test. Follicular aspiration for egg retrieval in all cases was performed laparoscopically. The finding that none of 200 consecutive transvaginal oocyte aspirations has resulted in severe ORSS led us to conclude that small follicles missed during laparoscopic aspiration may contribute to the develVol. 58, No.4, October 1992
opment of the syndrome. These little follicles may continue to grow after establishment of a pregnancy secondary to hCG stimulation. This conclusion is in agreement with findings reported by Tal et al. (6), who found a correlation between the number of immature follicles and ORSS. With this background and ultrasonographic findings suggesting nonhemorrhagic cysts in the ovaries of these patients with ORSS after IVF or GIFT, we proceeded with aspiration of these cysts along with any ascitic fluid in women who presented to us with this syndrome after assisted reproductive procedures. In the first patient in whom such a procedure was performed, large cysts along with ascitic fluid were aspirated, leaving behind the smaller cysts when the cyst diameter was 50% incidence reported in the literature. Abdominal and vaginal paracentesis has been reported as a means to reduce patient's symptoms and cut the vicious circle and prevent serious complications (1). Although the average hospital stay has dropped from approximately 30 days to 15 days with this procedure, patients were usually still symptomatic, and the aspiration process would have to be carried out very frequently, sometimes more than once or twice per day. The latter may be because of the fact that the disease origin is in the ovaries, and abdominal paracentesis will not actually cure the disease but would relieve the symptoms. In our series, aspiration of the ovarian cysts not only relieved the symptoms but also shortened the disease process, interrupted progression of the disease, and allowed outpatient treatment. Moreover, women with ORSS after aspiration of the ovarian cysts do not have to be immobilized to avoid cyst rupture. The immoFakih and Bello
Communications-in-brief
831
bilization may increase the risk of vascular thrombosis' especially in those women who in the severe form of OHSS have concomitant hemoconcentration. SUMMARY
Ultrasonographically guided transvaginal aspiration of ovarian cysts in women with severe OHSS after GIFT or IVF was safe and has resulted in immediate relief of symptoms, a shorter disease process, and outpatient treatment. The patients were allowed to go back to normal activity after the procedure. The progression of the disease was interrupted and six of seven patients carried beyond 20 weeks' gestation. Key Words: Severe ovarian hyperstimulation syndrome, cyst aspiration, ascites, in vitro fertilization, gamete intrafallopian transfer.
832
Fakih and Bello
Communications· in-brief
REFERENCES 1. Aboulghar MA, Mansour R, Serour GI, Amin Y. Ultrasoni· cally guided vaginal aspiration of ascites in the treatment of severe ovarian hyperstimulation syndrome. Fertil Steril 1990;53:933-5. 2. Golan A, Ron-EL R, Herman A, Soffer Y, Weinraub Z, Capsi E. Ovarian hyperstimulation syndrome: an update review. Obstet Gynecol Surv 1989;44:430-40. 3. Schenker J, Polishuk W. The role of prostaglandins in ovarian hyperstimulation syndrome. Eur J Obstet Gynecol Reprod Biol1976;6:47-52. 4. Knox G. Antihistamine blockade of the ovarian hyperstimulation syndrome. Am J Obstet Gynecol 1974;118: 992-4. 5. Glorioso N, Atlas S, Laragh J. Prorenin in high concentrations in human ovarian follicular fluid. Science 1986; 233:1422-4. 6. Tal J, Paz B, Samberg I, Lazarov N, Sharf M. Ultrasonographic and clinical correlates of menotropin versus sequential clomiphene citrate: menotropin therapy for induction of ovulation. Fertil Steril 1985;44:342-9.
Fertility and Sterility
Vol. 58, No.4, October 1992
Copyright" 1992 The American Fertility Society
Printed on ocw·tree paper in U.S.A.
Ovarian cyst aspiration: a therapeutic approach to ovarian hyperstimulation syndrome
Hasan Fakih, M.D.*t Sandra Bello, B.S.:\: Michigan State University, East Lansing, and Saginaw Cooperative Hospitals, Inc., Saginaw, Michigan
Ovarian hyperstimulation is an iatrogenic complication of multiple follicular stimulation with menotropic medications before in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT) procedures. Severity of the syndrome can range from mild to severe with symptoms of ovarian enlargement, ascites, pleural effusion, and complications of hemoconcentration, hypercoagulability, and hypovolemia. These complications can be potentially lifethreatening. The pathophysiology of this syndrome is unclear, and medical management has traditionally been conservative and supportive consisting of bedrest, replacement of fluids, and volume expanders. Abdominal paracentesis has been introduced as a means to improve the symptoms of ascites and probably shorten the duration of the illness (1). Pregnancy outcome is usually poor with >50% resulting in spontaneous miscarriages (2). We are reporting a new approach for the treatment of ovarian hyperstimulation syndrome (OHSS). Transvaginal ultrasound (US)-guided aspiration of ovarian cysts and ascitic fluid was performed in seven women with OHSS with good outcome. MATERIALS AND METHODS
The diagnosis of severe OHSS was made when the patients presented after GIFT or IVF with pelvic discomfort, and pelvic US documented the presence Received December 9, 1991; revised and accepted May 27, 1992.
* Department of Obstetrics and Gynecology, Michigan State University. t Reprint requests: Hasan Fakih, M.D., Department of Reproductive Endocrinology and Infertility, Saginaw Cooperative Hospitals, Inc., 1000 Houghton Avenue, Saginaw, Michigan 48602. :t: Michigan State University medical student. Vol. 58, No.4, October 1992
of ascites and enlarged cystic ovaries with an ovarian diameter > 12 cm. Additional symptoms included shortness of breath and, in some, decreased urine output. All patients had a positive pregnancy test. Seven were treated with transvaginal aspiration of ovarian cysts and of ascitic fluid. The aspiration was performed in the operating room under sterile conditions. Before aspiration, 500 cc of a plasma expander was infused over 1 hour (Table 1). An additional 500 to 1,000 mL were then infused during the procedure. The patient was then placed in an antiTrendelenberg position to facilitate pooling of ascitic fluid in the pelvis. The aspirating needle was introduced transvaginally into the cul-de-sac under direct US guidance, and the ascitic fluid was aspirated. The needle was directed into the ovarian cysts, and these were aspirated sequentially. All accessible cysts, regardless of size, were aspirated from both ovaries. The patient was given 50 to 100 mg of progesterone (P) in oil intramuscularly (1M) and was monitored for 1 hour in the recovery room. If stable, she was transferred to the outpatient department for 2 more hours of observation and was discharged home upon documentation of stable vital signs, with normal serum electrolytes, kidney function tests, and coagulation profile. The patients were maintained on P supplementation for 2 more weeks. They were monitored weekly for serum estradiol, P, and human chorionic gonadotropin (heG) levels along with pelvic US assessment of the pregnancy and of ovarian size. The patients were instructed to contact us upon development of pelvic discomfort or vaginal bleeding. RESULTS
Since May 1987, eight women were diagnosed with severe OHSS among 800 procedures for an incidence Fakih and Bello Communications-in-brief
829
Table 1
Clinical Data of Women With Severe OHSS Treated by Transvaginal Ovarian Cyst Aspiration
Case no.
Amounts of fluid aspirated
1
a.2,000 b.2,000 c.2,100 a.2,000 a. 500 a. 500 a.l,400 b.l,500 c.l,700 a.l,500 a.3,000
Plasma expander
Luteal support postaspiration
Length of hospital stay
a. None b. None c. P 50:1: a. P 100:1: a. None b. P 100:1: a. P 50:1:
a. 7§ b. 7§ c. Outpatient Outpatient Outpatient Outpatient Outpatient
Single term delivery Miscarried Twin term delivery Twin term delivery
b. P 50:1: c. P 50:1: a. P 50:1:
Outpatient Outpatient Outpatient
Twin preterm delivery Twin progressing pregnancy
Outcome
mL
2 3 4 5 6 7
a. None b. Plasmanate-l,500* c. Plasmanate-l,500* a. Rheomacrodex-2,000* a. None b. Plasmanate-500* a. Plasmante-l,OOO* b. Plasmante-l,OOO* c. Albumin-25 gt a. Dextran 40-500* a. Dextran 40-1,000*
* Gram. t Milliliter.
:1: Milligram 1M. § Days.
of 1 %. The first patient was treated symptomatically, and the pregnancy ended in a spontaneous miscarriage at 8 weeks of gestation. Ovarian cysts formed as part of the complex of severe ORSS in our patient population were noted to be ultrasonographically clear. This finding indicated that these are follicular rather than luteal in origin. Moreover, most of the presenting symptoms in women with severe ORSS are known to be related to ovarian enlargement. The above findings prompted us to proceed with aspiration of ovarian cysts in all subsequent patients with the diagnosis of severe ORSS. The first transvaginal aspiration of ovarian cysts for the treatment of severe ORSS was performed in September 1988. The patient related immediate relief of symptoms without any complications and thereafter had a normally progressing pregnancy. In this first patient, the smaller ovarian cysts were intentionally avoided during the aspiration procedure. She later required two additional aspiration procedures 1 week apart because of recurrence of symptoms and the findings of ovarian enlargement by pelvic US. In subsequent patients, however, all accessible ovarian cysts, regardless of size, were aspirated, and only one of six patients required additional aspiration. All subsequent procedures were performed on an outpatient basis. None of the patients developed any complications related to the procedure in the immediate postoperative period or later on during the pregnancy. The average age of the patients was 25.2 years. All women had laparoscopic egg retrieval. The presenting symptoms included abdominal distention, bloating, and pelvic pain along with a positive pregnancy test. Three women complained of shortness 830
Fakih and Bello
Single term delivery
Communications-in-brief
of breath. On pelvic US scanning, they all had enlarged ovaries, 12 cm or greater in diameter, along with ascitic fluid in the pelvic cavity. Cases 1, 5, 6, and 7 had concomitant hemoconcentration (hematocrit > 42). Patients 1 and 4 had elevated liver enzyme levels. Serum sodium levels were low or low normal in all patients. Platelet counts were elevated (>500,000) in cases 5 and 7, respectively. None of the patients had abnormal coagulation profiles. Table 1 summarizes the treatment instituted and outcome in these patients. An average of 1,700 cc of fluid was aspirated per patient. Marked improvement in all patient's symptoms immediately after aspiration of fluid was observed. All patients had normal serum electrolytes, kidney function tests, and coagulation profiles before discharge. Abnormal liver functions persisted for an additional 2 to 4 weeks. Patients were followed by weekly US assessments of ovarian size, ascitic fluid volume, and fetal viability. Five of seven patients had normal ovarian size on follow-up with minimal ascitic fluid. All five women had persistent relief of pelvic discomfort and dyspnea. The remaining two patients were readmitted for aspiration because of accumulation of ascitic fluid and recurrence of symptoms. Except for our first ovarian aspiration case, the rest of the patients were treated on an outpatient basis. All patients received P suppositories for luteal support. Among the seven cases in whom ovarian cyst aspiration was performed, all, except case number 3, received P 1M after aspiration. Incidentally, this pregnancy ended with a spontaneous miscarriage, although good fetal heart activity could be seen until 4 weeks after aspiration. As can be seen in Table 1, Fertility and Sterility
all pregnancies except one carried beyond 20 weeks' gestation. DISCUSSION
Ovarian hyperstimulation syndrome is a wellknown side effect of controlled ovulation induction. With the introduction of IVF and related technologies, the number of women hyperstimulated with menotropins is increasing substantially all over the world, and this has resulted in an increased incidence of this syndrome (2). The syndrome in its severe form is reported to occur in 0.008% to 10% of stimulated cycles. Severe ORSS usually occurs in conceptual cycles, and >50% of these will end in a spontaneous miscarriage (2). Severe ORSS is a life-threatening condition, and patients will need hospitalization because the condition may rapidly deteriorate. The abdomen is usually very distended and tense with the ovaries larger than 12 cm in diameter. An acute fluid shift of the intravascular space may result in ascites, hydrothorax, and generalized edema. This fluid shift is caused by an increase of the capillary permeability, allowing fluid escape into the third space leading to ascites, pleural effusion, hypovolemia, and hemoconcentration with electrolyte imbalance. This may progress rapidly to hypovolemic shock, oliguria, and even coagulation disorders and thromboembolic phenomena. In a few cases, thromboembolic incidences were reported resulting in death (2). It is believed that this fluid shift is mediated by a vasoactive substance secreted by the ovaries. Estrogen, prostaglandins, histamine, and prorenin have been proposed as possible mediators (3-5). Aspiration of the ovarian cysts in women with severe ORSS may reduce the ovarian production of these hormones, thus reducing the stimulus propagating the disease process. Ovarian hyperstimulation syndrome is known to occur in spite of aspiration of ovarian follicles for the purpose of IVF or the GIFT procedure. In our experience of 800 consecutive controlled ovarian hyperstimulation cycles for the purpose of assisted reproductive technologies, eight patients fulfilled the criteria of severe ORSS. This complication in our series has occurred only in women with a positive pregnancy test. Follicular aspiration for egg retrieval in all cases was performed laparoscopically. The finding that none of 200 consecutive transvaginal oocyte aspirations has resulted in severe ORSS led us to conclude that small follicles missed during laparoscopic aspiration may contribute to the develVol. 58, No.4, October 1992
opment of the syndrome. These little follicles may continue to grow after establishment of a pregnancy secondary to hCG stimulation. This conclusion is in agreement with findings reported by Tal et al. (6), who found a correlation between the number of immature follicles and ORSS. With this background and ultrasonographic findings suggesting nonhemorrhagic cysts in the ovaries of these patients with ORSS after IVF or GIFT, we proceeded with aspiration of these cysts along with any ascitic fluid in women who presented to us with this syndrome after assisted reproductive procedures. In the first patient in whom such a procedure was performed, large cysts along with ascitic fluid were aspirated, leaving behind the smaller cysts when the cyst diameter was 50% incidence reported in the literature. Abdominal and vaginal paracentesis has been reported as a means to reduce patient's symptoms and cut the vicious circle and prevent serious complications (1). Although the average hospital stay has dropped from approximately 30 days to 15 days with this procedure, patients were usually still symptomatic, and the aspiration process would have to be carried out very frequently, sometimes more than once or twice per day. The latter may be because of the fact that the disease origin is in the ovaries, and abdominal paracentesis will not actually cure the disease but would relieve the symptoms. In our series, aspiration of the ovarian cysts not only relieved the symptoms but also shortened the disease process, interrupted progression of the disease, and allowed outpatient treatment. Moreover, women with ORSS after aspiration of the ovarian cysts do not have to be immobilized to avoid cyst rupture. The immoFakih and Bello
Communications-in-brief
831
bilization may increase the risk of vascular thrombosis' especially in those women who in the severe form of OHSS have concomitant hemoconcentration. SUMMARY
Ultrasonographically guided transvaginal aspiration of ovarian cysts in women with severe OHSS after GIFT or IVF was safe and has resulted in immediate relief of symptoms, a shorter disease process, and outpatient treatment. The patients were allowed to go back to normal activity after the procedure. The progression of the disease was interrupted and six of seven patients carried beyond 20 weeks' gestation. Key Words: Severe ovarian hyperstimulation syndrome, cyst aspiration, ascites, in vitro fertilization, gamete intrafallopian transfer.
832
Fakih and Bello
Communications· in-brief
REFERENCES 1. Aboulghar MA, Mansour R, Serour GI, Amin Y. Ultrasoni· cally guided vaginal aspiration of ascites in the treatment of severe ovarian hyperstimulation syndrome. Fertil Steril 1990;53:933-5. 2. Golan A, Ron-EL R, Herman A, Soffer Y, Weinraub Z, Capsi E. Ovarian hyperstimulation syndrome: an update review. Obstet Gynecol Surv 1989;44:430-40. 3. Schenker J, Polishuk W. The role of prostaglandins in ovarian hyperstimulation syndrome. Eur J Obstet Gynecol Reprod Biol1976;6:47-52. 4. Knox G. Antihistamine blockade of the ovarian hyperstimulation syndrome. Am J Obstet Gynecol 1974;118: 992-4. 5. Glorioso N, Atlas S, Laragh J. Prorenin in high concentrations in human ovarian follicular fluid. Science 1986; 233:1422-4. 6. Tal J, Paz B, Samberg I, Lazarov N, Sharf M. Ultrasonographic and clinical correlates of menotropin versus sequential clomiphene citrate: menotropin therapy for induction of ovulation. Fertil Steril 1985;44:342-9.
Fertility and Sterility
