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Journal of Experimental Medical & Surgical Research Cercetãri Experimentale & Medico-Chirurgicale Year XVII · Nr.1/2010 · Pag.18 - 22 JOURNAL of Experimental Medical Surgical R E S E AR C H EVOLUTION OF PREGNANCIES IN PACIENTS WITH OVARIAN HYPERSTIMULATION SYNDROME (OHSS) L. Bran, L. Stelea, D.M. Anastasiu, D. Bran, I. Munteanu1 SUMMARY: The ovarian hyperstimulation syndrome is a major complication that occurs in controlled ovarian stimulation. In the present study we monitored the evolution of pregnancies following In Vitro Fertilization (FIV/ET) after previously undergoing a controlled ovarian stimulation, complicated by the occurrence of the ovarian hyperstimulation syndrome. The studied group was represented by a number of 45 patients, age between 28 and 41 yeas old, over a period of three years (2005-2008), with pregnancies resulted after a controlled ovarian stimulation associated with a mild (69 %) or moderate type of ovarian hyperstimulation syndrome (31%). The first therapeutic approach was of abeyance, keeping the patient under observation: blood pressure, pulse, weight, abdominal circumference, diuresis for cases with a mild hyperstimulation; as for cases of moderate hyperstimulation, besides the parameters previously measured, we also monitored the biochemical parameters, as well as the quantity of ascitic fluid in the Douglas pouch. The cases had a favorable evolution, none of the patients required a pregnancy interruption. Assessments are to made concerning the therapeutic behavior and the data regarding the evolution of the pregnancy. Keywords: ovarian hyperstimulation syndrome, pregnancy, ascitic fluid. EVOLUTIA SARCINILOR LA PACIENTE CU SINDROM DE HIPERSTIMULARE OVARIANA Received for publication: 01.12.2009 Revised: 14.02.2010 Rezumat: Sindromul de hiperstimulare ovarianã este o complicaþie majorã în cadrul stimulãrii ovariene controlate. In studiul de faþã s-a urmarit evoluþia sarcinilor obþinute prin Fertilizare in Vitro (FIV/ET) dupã ce, în prealabil s-a efectuat o stimulare ovarianã controlatã, complicatã cu sindromul de hiperstimulare ovarianã. Lotul luat in studiu a fost reprezentat de un numar de 45 de paciente cu vârsta cuprinsã între 28 si 41 de ani, pe o perioadã de trei ani (2005-2008), cu sarcini obþinute post stimulare ovarianã controlatã asociate cu o forma usoarã (69 %) sau moderatã de sindrom de hiperstimulare ovarianã (31%). Atitudinea terapeuticã de primã intentie a fost de expectativã, pacienta fiind monitorizatã: T.A, puls, greutate, circumferinþa abdominalã, diureza în cazurile de hiperstimulare usoarã; în cazul prezenþei hiperstimularii moderate la parametrii monitorizaþi anterior s-a adaugat urmarirea parametrilor biochimici cât si a cantitaþii de lichid de ascitã din Douglas. Evolutia cazurilor a fost favorabilã, nefiind necesarã la nici una dintre paciente intreruperea cursului sarcinii. Se fac aprecieri asupra conduitei terapeutice si a rezultatelor obtinute privind evolutia sarcinii. 1. - U.M.F. „Victor Babes” Timisoara Correspondence to: Lavinia Bran. Tel. 0745091202, E-mail: [email protected], Timisoara str. V. Braniste nr. 5 jud. Timis 18 INTRODUCTION The ovarian hyperstimulation syndrome (OHSS) represents the most important complication of the ovarian stimulation treatments used in cases of human assisted reproduction techniques (artificial insemination, in vitro fertilization/embriotransfer). Any protocol of ovarian stimulation can lead to an ovarian hyperstimulation syndrome. The ovarian hyperstimulation syndromes can be of various degees, depending on the symptom complex developed by the pacient. Degree I patients (mild hyperstimulation) display abdominal discomfort and an increase of the both ovaries in dimensions on ultrasonography, with a diameter of up Degree II is one of moderate hyperstimulation. The patietiens generally display abdominal discomfort, gastrointestinal symptoms, abdominal pains, meteorism (bloated), bowel movements disturbances and nausea, vomiting and diarrhea. The sudden increase of weight, over 3 kg, can be considered an early sign of moderate hyperstimulation. From the ultrasonographic point of view, ascites and an increase of the ovaries volume can be noticed, with a diameter of up to 12x12 cm. The complete blood count and the biochemical parameters are between the normal limits or slightly modified. Degree III of ovarian hyperstimulation is a severe type and is characterized by the presence of ovarian cysts of significant dimensions with apparence of ascites and, in OHSS and pregnancyes OHSS middle type to 5x5 cm, multiple follicles and corpus luteum cysts. The serum levels of estradiol have values higher than 3.000pg/ml and those of progesterone are over 30pg/ml during the initial lutheal phase. The urinary levels of estrogen have values higher than 150mg/24hours and those of pregnandiol are over 10mg/24 hours. OHSS midle type some cases, hydrothorax and hydropericardium. In extreme cases patients may develop hemoconcentration, increase blood viscosity and thromboembolic events, hydro-electrolite disturbances, hypovolemia and even hypovolemic shock. The severe type is represented by serious complications such as respiratory failure, and thromboembolic events. 19 MATERIALS AND METHODS syndrome following the controlled ovarian stimulation. Out of group of 61 patients: 42 (69 %) developed a mild type of ovarian hyperstimulation syndrome out of whom 28 (66,6 %) had positive b-hCG and 14 (33,3 %) had a negative b - hCG. - 19 (31 %) developed a moderate type of ovarian hyperstimulation syndrome out of whom 17 (89,4 %) The present study was conducted on a group of 45 (2,91 %) pregnant women with ovarian hyperstimulation syndrome from a group of 1544 patients who were enrolled in the Human Assisted Reproduction program in our clinic during 2005-2008. The age of the patients was between 28 and 41 years old, with a mean age of 34,5 years old. The criteria for the study were represented by the presence of ovarian hyperstimulation syndrome in different degrees in patients who had positive b-hCG. The mean period of infertility of patients who were enrolled in the present study was of 6,5 years, 27 (60 %) of them presenting infertility for less than 6 years, and 18 (40 %) suffering from infertility for more than 6 years. The causes of infertility were: - chronic anovulation in 29 patients (64 %) - male factor in 8 patients (18 %) - no apparent cause in 8 patients (18 %) had a positive b-hCG and 2 (10,5 % ) had a negative The glycemia levels were between the normal limits in b-hCG. all patients. The mild type of ovarian hyperstimulation syndrome Out of the 45 pregnant patients who developed ovarian generally developed in patients with a negative b-hCG or hyperstimulation syndrome, 15 patients (33,3 %) had it was metter of bio-chemical pregnancy. regular menstrual cycles and the other 30 (66,6 %) Out of the patients with positive b-hCG 28 (62,2 % ) developed a mild form of hyperstimulation and 17 ( 37,7 % ) developed a moderate form of hyperstimulation. 30 28 25 20 14 15 B-hCG pozitive B-hCG negative 10 5 0 OHSS mild type displayed disturbances of the menstrual cycle: oligomenorrhea 17 (57 %), amenorrhea 6 (20 %), hipomenorrhea 4 (13 %), as well as polymenorrhea 3 (10 %). RESULTS AND DISCUSSION All of the 45 pregnant patients with ovarian hyperstimulation syndrome were chosen out of a group of 61 patients (3,95 %) who had polycystic ovary 20 18 16 14 12 10 8 6 4 2 0 17 B-hCG pozitive B-hCG negative 2 OHSS midle type OHSS moderate type As for the behavior, the pregnant patients with a mild form of hyperstimulation and who displayed discrete abdominal discomfort, increase of ovaries’dimensions with multiple follicles and corpus luteum cysts, estradiol higher than 3.000pg/ml, progesterone higher than 30 pg/ml, were observed at least two weeks, being monitored for their body weight, abdominal circumference, diuresis, bio-chemical parameters. In these cases, the hyperstimulation presented a remission in 5-7 days and the pregnancy evolution was favorable. In those cases of pregnancy associated with moderate ovarian hyperstimulation syndrome the patients were advised to rest, to oral hydratation; their diuresis and body weight were closely monitored. Most of the cases presented a spontaneous resolution. Out of the study group 17 (37,7 % ) cases of pregnancy displayed moderate ovarian hyperstimulation syndrome. All of them presented ascitic fluid in the Douglas pouch, urinary retention, difficult respiration, significant increased weight, increase of the abdominal circumference, as well as modifications of the bio-chemical samples. In 3 (6,66 %) cases the quantity of ascetic fluid in the Douglas pouch was very high, the patients having to undergo a transvaginal puncture, 500ml/day in 4-6 days. Also 2 patients (4,44 %) presented urine retention; by monitoring the diuresis, elimination of 100-120ml/day was observed, considering the fact that a quantity of 2000-2500ml of liquid/day was administrated. In these cases loop diuretics were administered (furosemide). All cases of moderate ovarian hyperstimulation syndrome were trated with Albumin in order to re-balance the hidro-electrolite level. The remission of the symptom complex varied from case to case, sometimes reaching 30 days. No case of pregnancy associated with severe hyperstimulation was registered. Out of all cases included in the study, there was no pregnancy loss, all of them presenting a favorable evolution. Any case of pregnancy associated with ovarian hyperstimulation syndrome do not need for pregnancy's interruption ( no case threatened the patient’s life). From the total of 45 patients, a number of 34 (75,5 % ) presented unique pregnancies, and gave birth to alive, eutrophic children. A number of 5 (11,1 % ) patients presented triple pregnancy, from which 4 (8,88 % ) gave birth prematurely between the weeks 32-34 of gestation with a good evolution of children; in one single case (2,22% ) the birth took place at 28 weeks with postpartum death of the children. Tween pregnancy appeared at a number of 6 (13,3 % ) patients, they gave birth bewteen 34 and 35 weeks of gestation, to alive children with a good evolution. CONCLUSIONS 1. The ovarian hyperstimulation syndrome was present at patients with polichystic ovarian syndrome who have undergone a controlled stimulation. 2. It is of high importance that the patients with excessive ovarian response to be closely monitorised. 3. The ovarian hyperstimulation syndrome is more frequent in the case of patiens with positive b-hCG. 4. During the analysis of the ovarian hyperstimulation syndrome present in pregnant patients, it is higly important to monitorise all the parameters in order to keep the volemia in balance and to correct the hidro-electrolyte disturbances. 5. A treatment protocol must be used for patients who have undergone a process of In Vitro Fertilization/Embrio Transfer. 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