Samir Fouad Abdel Aziz, MD

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Objective: To evaluate the effect of immediate postpartum curettage upon  maternal recovery from severe Preeclampsia.

Methods: Sixty parturient women with severe Preeclampsia were randomly  assigned to either undergo ultrasound directed curettage following delivery  (n=30)or to have no curettage (controls=30).

Results: Subjects who underwent immediate postpartum curettage had a  significant decrease in mean arterial pressure at 16 hours post delivery  (p<0.0002). The mean urine output after uterine curettage was significantly  greater after the first 12 hours post delivery compared to controls (p<0.0002).  Platelet count increased in the curettage group from 12 to 24 hours following  curettage, while controls exhibited a decrease in the platelet count from 12 to  24 hours (p<0.02).

Conclusion: Immediate puerperal uterine curettage of the parturient with  severe Preeclampsia appears to accelerate disease recovery with no adverse  sequelae.

Preeclampsia is considered as an endothelial cell disorder observed only in  the pregnant human female(1). Defined classically as the development of  hypertension, proteinuria and/or edema in the second half of pregnancy in a  woman who has previously been normotensive and otherwise clinically well (2). It  occurs in 7% of all pregnancies and is associated with increased maternal and  perinatal morbidity and mortality (3).

There are many maternal complications of Preeclampsia such as abruptio  placenta, thrombocytopenia, hepatic hemorrhage and rupture, eclampsia,  disseminated intravascular coagulation, stroke, intracerebral hemorrhage, acute  renal failure, and the syndrome of hemolysis, elevated liver enzymes and low  platelet count. (HELLP).(4)

Accelerated recovery from this disease process following delivery could avert  these complications and shorten the time required for intensive care and  hospitalization.

The subjects of this study were 60 pregnant women who presented to labor and  delivery department, Al-Hussein University Hospital, with physical findings  consistent with severe Preeclampsia.

  Severe Preeclampsia was defined as combinations of the following:1-Blood pressure at least 160/110mmHg on two occasions at least 6 hours  	apart.
 	2-At least 3+ proteinuria on a semi qualitative assay
 	3-Less than 400 ml of urine output over 24 hours.  	

Because hypertension, proteinuria and oliguria are not always present  	consistently and concurrently in patients with severe Preeclampsia,  	additional criteria involved verifying the diagnosis of severe disease.  	These include:1-Cerebral or visual disturbances such as altered consciousness,  	headaches, scotoma, or blurred vision.
 	2-Pulmonary edema or cyanosis.
 	3-Epigastric or right upper quadrant pain
 	4-Impaired liver function of unclear etiology
 	5-Thrombocytopenia, or
 	6-Fetal growth retardation. 

Subjects signed informed consent and a computer-generated random card was  drawn and the patients were assigned to receive immediate postpartum curettage  or no curettage.

At admission, evaluation included mean arterial pressure (MAP), hemoglobin  and hematocrit, urine dipstick for presence of proteinuria, quantitative  platelet count, uric acid and serum creatinine, liver function tests,  neurological examination and Ophthalmological examination of the fundus.

Thirty patients underwent uterine curettage after vaginal or caesarian  delivery. At Caesarian , the presumed area of the decidua basalis was curetted  with large banjo curette (fig.1). Patients who delivered vaginally were sedated  with intravenous butorphanol tartrate (Stadol, Bristol Laboratories, Evansville,  IN, USA) and promethazine hydrochloride (Phenergan,Wyeth, Ayerst,  Philadelphia,PA) and underwent ultrasound guided curettage using large Banjo  curette (fig.1).

All curettage specimens were sent for pathological examination.

During the immediate puerperium, all subjects were observed in the obstetric  recovery room until disease remission was apparent. Intensive postpartum  surveillance maintained for 24 hours,and included hourly measurement of MAP,  hourly urine output, hemoglobin and hematocrit with platelet count every 6  hours, and uric acid and creatinine assessment at 12 and 24 hours.

All medications given in the obstetric recovery room were recorded. All women  received magnesium sulfate by continuous IV infusion at a rate of 1.3g/hour  during the study interval. None of the patients received fluid challenge in the  obstetric recovery area. Discharge criteria from this area included:1)adequate  diuresis (output>100ml/hour sustained for at least 2 consecutive hours), 2)  blood pressure control, with diastolic values below 100mmHg and systolic below  160mmHg, and 3), rising platelet count above 50,000/ml.

The time each patient spent in the obstetric recovery room were recorded.

Longitudinal data between groups were analyzed by repeated measure analysis  of variance over time. Grouped demographic data were analyzed by X2 or Fisher  exact test as appropriate. Group means were analyzed by unpaired t test. Data  are expressed as mean ± Standard deviation (SD). P<0.05 was considered  statistically significant.

The age, number of pregnancies, and duration of gestation were similar in  both groups (table 1). The initial MAP in all patients was more than 110 mmHg.

As shown in table 1, laboratory indices of renal function, uric acid and  platelet count was similar in both groups.

On pathological examination, the curettage specimens revealed many decidua  with minimal placental tissue.(fig.2,3)

The MAP of the curettage group was significantly reduced compared with  controls at each 12 hours intervals after delivery (fig.4) with the largest  difference at 14 hours postpartum (p<0.0002).

Mean urine output for the curettage group was significantly greater than for  the non-curettage group at 4-hour interval postpartum (fig.5). The smallest  difference between both groups was observed at 4 hours and the largest  difference at 20 hours postpartum (p<0.0002).

Platelet counts also demonstrated a significant change over time after  delivery (fig.6) with the concentration increasing from 159,000/ml at 12 hours  to 162,000/ml at 24 hours postpartum in the curettage group. On contrast, the  non-curettage group had a mean platelet count of 148.500/ml at 12 hours  postpartum, decreasing to 135,000/ml at 24 hours (p<0.05).

Mean serum levels of uric acid, urea and creatinine were not significantly  different between both groups at 12 and 24 hours postpartum (table 2).

Also, there was no significant difference in the frequency of medications  administered to either group. In the group with curettage 8 patients had  eclamptic fits before delivery, none of them had further fits after delivery and  curettage, while 2 out of 6 patients with antepartum fits had further fits after  delivery in the non-curettage group.

There were no complications from curettage. Twenty-two patients who underwent  curettage were eligible for discharge from the obstetric recovery room at 24  hours, compared with nineteen controls, a non significant difference.

Follow-up for all curettage patients revealed that 11 had onset of  menstruation within 6 weeks and 19 had had lactation amenorrhea, non had  infection or hemorrhagic complications after the curettage.

For control group 14 had onset of menstruation within 6 weeks of delivery and  16 had lactation amenorrhea.

Demographic Characteristics and admission criteria

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Subjects who underwent immediate postpartum curettage had a significant decrease in mean arterial pressure at 16 hours post delivery (p

Effect of Immediate Postpartum Curettage on the Recovery of Severe Preeclampsia

 To compare pregnancy rate in women with polycystic ovary syndrome(PCOS) resistant to clomiphene citrate, using different methods of treatment.
 
 

 One hundred infertile women known to have PCOS and failed to conceive with one-year clomiphene citrate treatment.
 
 

 Women randomly classified into 5 groups, each comprised 20 cases. Group (1) received clomiphene citrate plus human menopausal gonadotrophines (HMG) plus human chorionic gonadotrophins(HCG). Group (II) received HMG + HCG. Group (III) received pure FSH plus HCG. Group (IV) received LHRHa plus HMG. Group (V) subjected to laparoscopic ovarian drilling using diathermy.
 
 

 In group (I) four out of 20 women (20%) responded to treatment and became pregnant in 60 treatment cycles (6.66%). In Group (II) six women (30%) had pregnancy in 60 cycles of treatment (10%). In the third group pregnancy occurred in 3 women (15%) with 60 treatment cycles (5%). In the fourth group eleven women became pregnant (55%) during the same treatment cycles (18%), this was statistically significant when compared to group I and III. In the laparoscopic group 9 (45%) women had pregnancy during three months after ovarian drilling.
 
 

 Several alternative ovulation induction methods are available, the use of LHRH analogue combined with HMG/HCG had better results and laparoscopic diathermy can be the second in rank in the selection of treatment.


 Polycystic ovary syndrome is characterized by enlarged ovaries, multiple peripherally arranged cysts and increased stromal density(1). Polycystic ovary syndrome is responsible for approximately 25-30% of infertility

  in women, which is mainly anovulatory(2). Ovulation can be induced with antiesterogens in many women but a proportion fail to respond and even  in those who ovulate, the pregnancy rate is often low and the miscarriage rate is high. However, treatment with  human menopausal gonadotrophins may be successful but extremely demanding for women and for the clinic, and there is a  significant risk of hyperstimulation and multiple pregnancy even with intensive monitoring(3). Pulsatile luteinizing  hormone releasing hormone (LHRH) therapy has been used but the results have been disappointing and miscarriage rate is high(4).  However, the use of LHRHa in down regulation mechanism (pituitary  desensitization) gave a rather good results with entire elimination of premature  luteinization and higher pregnancy rate(5).
 
 Wedge resection of the ovaries was used successfully in the management  of women with PCOS prior to the availability of anti-estrogens in the 1960, this treatment resulted in a high rate of  ovulation but was followed by significant formation of adhesions that prevented pregnancy from a few months after  the procedure was performed(6). Recently laparoscopic diathermy has been introduced as an alternative to wedge resection(7-10). The  advantages of this form of treatment are that it entails laparoscopy  rather than laparotomy and the scars are small. Ovulation has been found to  occur post operatively in more than 80% of women(7).
 
 These alternative methods of management of PCOS cases resistant to clomiphene citrate provoked us to study pregnancy rate with different methods of treatment.
 
 


 One hundred women with primary infertility and ultrasonic features of  polycystic ovaries(1) were selected for this prospective study. All had  oligomenorrhoea with or without hirsutism. Biochemically, all had an Lh/FSH ratio >3.
 
 All patients failed to conceive after one year of treatment with clomid. In all, fallopian tubes were patent, proved by HSG and laparoscopy, their husbands had normal semen analysis and no obvious cause of infertility apart from anovulation was found.
 
 All patients signed a consent to be involved in the study and they were randomly classified into 5 groups.
 
 Group I comprised 20 patients, received Clomid in a dose of 150 mg/day from day 3 through day 7 of the menstrual cycle

, human menopausal gonadotrophins (Pergonal, serono) started with an initial dose of 150 IU given I.M at day 5 of the menstrual cycle and the dose was adjusted according to ovarian response with the intention to obtain one or more mature follicles with follicular diameter greater than 17 mm and estradiol (E2) level >800 pg/ml. Treatment was monitored by ultrasound and serum assay for estradiol. Ultrasound was performed twice usually at day 10 and day 13, E2 estimation was performed at days 11,12, and 13. HCG injection (Profasi, serono) was given in a dose of 10,000 IU IM when we reached our criteria of ovulation and timed intercourse was requested post HCG by 24-36 hours.
 
 Group II comprised 20 patients who received Pergonal initially in 2 amps dose (300IU) and adjusted according to the ovarian response. Treatment started on day 3 of the menstrual cycle and the criteria and monitoring of ovulation followed the same protocol as in group I. Timed intercourse was requested 24-36 hours after HCG (10,000IU) injection.
 
 Group III also comprised 20 patients, received pure FSH (metrodin, 75 IU) started on day 3 of the menstrual cycle in dose of 2 amps which was increased or decreased according to the ovarian response. The same criteria and monitoring of ovulation were used in this group as previous groups. Timed intercourse was requested 24-36 hours after 10,000 IU injection of         HCG.
 
 Group IV included 20 patients, received LHRH agonist (superfact, Hoechst hounslow, uk). Nasal spray started on day 24 of the preceding cycle with one puff per nostril every 6 hours to deliver 100 ug. The drug was continued till day O (day of HCG administration). Pergonal was given on day 3 of the menstrual cycle with initial dose of 2 amps and the dose was adjusted according to the ovarian response. The same criteria and monitoring of ovulation was as previous and timed intercourse advised 24-36 hours post HCG injection (10,000IU).
 
 Group V Twenty patients had laparoscopic ovarian drilling using diathermy during the proliferative phase of the menstrual period. Diathermy was applied to each ovary for 4-6 seconds at a time in 4-8 separate places according to the ovarian size. All patients were followed for 3 months with no further treatment.
 
 


 A semi quantitative urinary test was performed 10 days after the expected date of next period or 24 days post HCG injection.
 
 


 Blood samples were collected in a dry plastic disposable syringe on heparinized tubes and then centrifuged. Plasma was taken for determination of E2, FSH and LH.
 
 E2 was measured by RIA using the method of Schmidt et al(11). LH was  determined by the heterologus ovine double antibody radioimmunoassay according to the method used by loudon et al(12). FSH was measured in  duplicate in single assay using an ovine radioimmunoassay method described by McNatty et al(13).
 
 
 


 All patients had primary infertility, where the duration of infertility is shown in table (1), in terms of mean and standard deviation, group V had a longer duration of infertility (10.2 ±5.3 years).
 
 The mean age and SD of the studied groups was also compared in table (1), group IV had the oldest patient with mean age and SD (36.4 ±1.9). None of these are statistically significant.
 
 The pretreatment hormonal levels of both the LH and FSH showed the characteristic feature of         PCO, where as seen in table (1) the LH is higher than the FSH by two or three times.
 
 In group I four out of the 20 cases (20%) responded to the treatment and became pregnant in a total of 60 treatment cycles (6.66%). In group II six women (30%) had pregnancy out of 20 women in 60 treatment cycles (10%). In the third group pregnancy was achieved in 3 out of 20 cases (15%) over 60 treatment cycles (5%). In group IV, 11 women became pregnant (55%) out of 20 women over 60 treatment cycles (18%), this was statistically significant (p<0.05) when compared to group I and also when compared with group II (p<0.02).
 
 In the fifth group nine women became pregnant (45%) over 3 months (60 cycles, 15%).


 Several alternative ovulation induction methods are available to women with clomiphene resistant anovulation associated with polycystic ovary

 syndrome (PCOS) but there are no accepted guide lines on the choice of treatment. 
 
 The use of HMG with clomiphene citrate to enhance follicular growth and increase its efficacy as in group I of this study is a known method. It is less expensive than the others but the pregnancy rate per cycle is and the use of LHRHa combined with HMG is statistically significant p<0.05 when both regimes were compared.
 
 The pregnancy rate in the second group (HMG+HCG) regime was 10% (pregnancy per treatment cycle) these results are less than the result of Farhi et al. 1993. When the pregnancy in this group compared with the other groups no statistically significance was found.
 
 The third group received FSH, there results as a pregnancy per treatment cycle was 5%, which is less than the pregnancy rate obtained by the Farhi et al, 1993, where they reported pregnancy rate 23%. However, this group results were significant when compared to group IV, (p<0.02).
 
 The fourth group LHRHa combined with HMG/HCG, gave a better results regarding pregnancy rate which might be explained because of the elimination of premature luteinization and prevention of the interference and interplay of the high LH which is a dominant feature in PCOS. Our results were similar to Farhi et al, 1993; and Wada et al, 1993. The results of the LHRHa group had a statistical significance when compared with group I and group III.
 
 The last group, where the laparoscopic drill was offered as a surgical line of treatment the current study results were less in terms of pregnancy per treatment cycles than the results of Armar and Lachalin, 1993 and Gjonneses, 1994.
 
 The laparoscopy group when compared to other groups no statistical significance was found but apparently the laparoscopy carries advantages over the other lines of treatment as the chance of recurrent spontaneous ovulation and repeated pregnancy allowing the women to lead a normal life with the stress of frequent hospital visits and no risk of         hyperstimulation.
 
 
         


 In conclusion we have shown that women with PCOS resistant to clomiphene citrate have had several alternative ovulation induction. The use of LHRHa combined with HMG/HCG has better results and laparoscopic diathermy can be the second in rank in the selection of the treatment.

1-Adams Frants,S, and Polson,DW. Multifollicular ovaries, clinical and endocrine features and response to pulsatile gonadotrphine releasing hormone. Lancet II, 1985, 1375-1378.

2-Clayton RN, Ogden V, and Hodgkinsonc. How common are polycystic ovaries in normal women and what is their significance for the fertility of populations. Clin.Endocrinol,1992, 39:623-632.

3-Amrar,NA, and Lacheline,GL. Laparoscopic ovarian diathermy: an effective treatment for antiestrogen resistant anovulatory infertility in women with polycystic ovary syndrome. Br. J. Obst.Gyn,1993, 100:161-164.

4-Eshel A, Abdal Wahib N, Armar NA, Abdams JM, Jacobs HS. Pulsatile luteinizing hormone releasing hormone therapy in women with polycystic ovary syndrome. Fertil. Steril, 1988, 49:956-960.

5-Farhi J, Homburg R, Lerner A, Ben Rafeal Z. The choice of treatment for anovulation associated with polycystic ovary syndrome following failure to conceive with clomiphene. Hum.reprod.,1993, 8:1369-1371.

6-Adashi EY, Rock JA, Guzick D, Went ZA, Jone GR, Joes HW. Fertility following bilateral ovarian wedge resection, a critical analysis of 90 consecutive cases of polycystic ovary syndrome. Fertil. Steril. 1981,36:320-325.

7-Gjnnaess,H. Ovarian electrocautery in treatment of women with polycystic ovary syndrome(PCOS): Factors affecting the results. Acta Obstet. Gynecol. Scand. 1994, 73:407-412.

8-Kovacs G, Buckler H, Bangah M. Treatment of anovulation due to polycystic ovarian syndrome by laparoscopic ovarian electrocautery. Br. J. Obst. Gyn. 1991,98:30-35.

9-Wada I, Matson PL, Tromp, SA and Berman BA. Assisted conception using buserelin and human menopausal gonadotrophins in women with polycystic ovary syndrome. Br. J. Obst.Gyn. 1993, 100:365-369.

10-Schmidt AM, Nadal Schmidt MJ, and Beamer NB. Serum concentration of oestradiol and progesterone during the normal oestrous cycle and early pregnancy in the loin. Journal of reproduction and fertility,1979,57:267-272.

11-Loudon AS, McLeod BJ, and Curleuris JD. Pulsatile secretion of LH during the preovulatory and luteal phases of oestrous cycle pero daird's deer kind. Journal of reproduction and fertility,1990, 89:663-670.

12-McNatty KP, Fisher M, Collins, Hudson NL, Heath DA, and Henderson KM. Differences in the plasma concentration of FSH and LH in ovarectomized Barooth FF and EWES. Journal of reproduction and fertility,1989, 85:705-713.

Polycystic ovary syndrome is characterized by enlarged ovaries, multiple peripherally arranged cysts and increased stromal density(1). Polycystic ovary syndrome is responsible for approximately 25-30% of infertility in women, which is mainly anovulatory(2). Ovulation can be induced with antiesterogens in many women but a proportion fail to respond and even in those who ovulate, the pregnancy rate is often low and the miscarriage rate is high.

Conception Rate in Polycystic Ovary Syndrome

Vitamin E (alpha-tocopherol) is  thought to play a role in several stages of carcinogenesis through its  contribution to immunocomptence, inhibition of mutation formation and  repair of membranes and DNA.

To evaluate the efficacy of vitamin E in treatment of cervical cancer precursor (Cervical Intraepithelial Lesion, CIN)

Prospective double-blind placebo controlled clinical trial.

Al-Hussein University Hospital, El-Darassa, Cairo.

The target population  was 100 women with biopsy confirmed Cervical Intraepithelial Neoplasia  I&II (CIN I & II). All women were from the same catchment     area (El-Darassa) with similar socioeconomic status. Patients signed  informed consent and serum was taken for vitamin E assay using high  pressure liquid chromatography, serum vitamin E measured at the start of  the study and at 6 months. Patients were randomly divided into four  groups. First group (group I) comprised 25 patients, received vitamin E  injection,100mg (0.33cc) intralesion every month under colposcopic  guidance. Second group (group     II, 25 patients) received placebo (o.33cc sterile saline)  Intralesion every month under colposcopic guidance. Third group (Group  III, 25 patients) received oral vitamin E 400mg daily for 6 months.  Fourth group (Group IV,25 patients) received oral placebo daily for 6  months.

Response rates were determined at 0, 3, 6, 9 and 12 months with cytology, colposcopy and/or biopsies.

Complete regression of CIN observed  in 44% (11/25) in group I, while in group II regression rate was     16% (4/25) which is statistically significant (P<0.05). Also the  duration taken for complete response was significantly higher in group I  than in group II (5.57

Regression rates in group III were higher 24% (6/25) than that in group         IV12% (3/25), but was not statistically significant.

Lesions with diameter <100mm2 showed  significant regression rates than those with diameters<100mm2. Serum  vitamin E was low in all groups and remained low except in group III it  was significantly higher than other groups after 6 months of treatment.

Injection of vitamin E locally in  Cases with CIN I & II gave good response rates and further studies  with larger and frequent doses are recommended.

Worldwide cervical cancer is second only to breast cancer as the most common malignancy in both incidence and mortality

The cervix is an ideal model for the study of  chemoprevention in humans. The evidence is strong that normal cervical  epithelium proceeds through a precancerous stage (Cervical  Intraepithelial Neoplasia) prior to the development of invasive cancer.
 
 Vitamin E is thought to play a role in several stages of carcinogensis  through its contribution to immunocomptence, inhibition of mutagen  formation and repair of membranes and DNA. The question as to whether  vitamin E can prevent or slow down carcinogensis has interested a number  of researchers during the past few years 

. It has been hypothesized that free  radical-initiated cell damage and particularly DNA damage, is involved  in the etiology of cancer, and that vitamin E, because of its properties  as an antioxidant and free radical scavenger, may play a role in the  prevention of cancer 

. Vitamin E is also thought to have other anticancer  effects. Animal and invitro studies suggest that vitamin E decreases  tissue susceptibility to malignancies in several stages of carcinogensis  by a number of ubiquitous mechanisms. These include inhibition or  blockage of formation of nitrosamines 

 or other mutagens or carcinogens from precursors via direct chemical interaction.

It has also been suggested that vitamin E inhibits  mutagens or carcinogens from reaching or reacting with target sites by  scavenging mutagens or by enhancing detoxification process. Furthermore,  the vitamin may prevent cancer progression by enhancing the immune  response to developing cancer cells and may cause tumor regression by  direct action on the cancer cells 

The aim of this study was to evaluate the efficacy of vitamin E in treatment of Cervical Intraepithelial Neoplasia.
 
 


 
 Hundred patients with cervical intraepithelial neoplasia I & II (CIN  I& II) included in this prospective study. All patients were  monogamy of similar socioeconomic background living in the same  catchment area (El-Darassa, Cairo).

Diagnosis of CIN was based upon cytology and confirmed  by colposcopically directed biopsies. For all patients colposcopic  examination was satisfactory with negative endocervical cytology and no  evidence of extension of the lesion into the vagina. All patients did  not receive therapeutic doses of vitamin E during the  previous 6 months  before start of study, they all signed informed consent and all had  Depo-Provera as a method for contraception during the study period.
 Serum was collected at the start of study and after 6 months to measure vitamin E using high pressure liquid chromatography

.
 Patients randomly divided into 4 groups:

Group I: (25 patients) received vitamin E injection  100mg into the lesion (0.33cc Vol., Kahira Pharmaceuticals &  Chemical Industries Co) monthly for 6 months using insulin syringe.

Group II: (25 patients) received warm saline  injection (0.33cc Vol.) into the lesion every month for 6 months using  insulin syringe.

Group III: (25 patients) received oral vitamin E 400IU/day (Kahira Pharmaceuticals & Chemical Industries Co) for 6 months.

Group IV: (25 patients) received oral placebo daily for 6 months.

Cervical lesion was mapped before, during and after the  study and data were recorded on modified colposcopic sheet. The diameter  of the lesion was measured by means of plastic ruler 2cm length glutted  perpendicular on the tip of a uterine sound.

Complete response was defined as complete regression of  the lesion on colposcopy and absence of dyskaryotic cells on cervical  smear as well as absence of residual CIN on biopsy at 12th. month.  Partial response referred to regression of the lesion by >50% as  measured by the product of the two largest perpendicular diameters of  the lesion and continued presence of dyskaryotic cells on smear. Lesion  showing reduction of <50% of diameter was considered stable.
 
 Clinical and laboratory data were tabulated and analyzed statistically  using IBM personal computer with statistical program Epi.Info.version  6.02. t-test used to compare means, chi-square to compare different  groups and Z-test to compare percentages with a significant level set at  P<0.05.
 
 


 
 Age of patients were comparable in all groups, with mean age (

The mean age ( SD) at first intercourse was comparable  in all groups with no statistical difference between groups, it was 17.8  (

1.8) years in groups I; II; II; and IV respectively.

No statistical difference between groups with regard to mean number of deliveries and mean duration of marriage. (

)
 
 The number of cases with CIN I were 16, 15, 13, and 14 in groups I, II,  II and IV respectively while the numbers of cases with CIN II were 9,  10, 12, and 11 in groups I, II, II, and IV respectively. Acetowhite  epithelium present in majority of cases with punctations and mosaic  blood vessels in some cases. (

)
 
 Complete regression of the lesion was seen in 44% (11/25) in group I, which was significant than group II, 16% (4/25) P<0.05.

Complete regression of the lesion was 24% (6/25) in group III while in group IV it was 12% (3/25), this was not significant (

).
 
 The duration for complete regression was significantly less in group I than in group II (5.75

The duration to achieve complete regression was  comparable in group III and IV (6.5 1.04 months vz 7 2.3 months  respectively). The duration to achieve partial response was comparable  in all groups. (

One patients in group I upstaged from CIN I to CIN II  and two patients from the control groups upstaged to CIN II and III  during the study period.
 
 Lesions with diameter <100mm2 significantly regressed completely than lesions with diameter>100mm2.(

Serum levels of vitamin E were low in all groups at the start of the study and showed significant rise in group III only after 6 months. (


 
 The association between vitamin E status and the risk of different sites  of cancer has been widely studied epidemiologically in the past 10  years. Most of the studies have concerned all sites of cancer or some of  the most incident cancer sites 

 (12, 13, 14, 15, 16, 17, 18, 19 ,20, 21, 22, 23)

Studies on cervical carcinoma have ,with few exceptions 

 revealed lower dietary intake of serum levels of vitamin E among cases of cervical dysplasia and cervical cancer 

Evidence from culture studies, animal models and  observational epidemiological studies that vitamin E may provide  protection against cancer has led to several clinical intervention  trials being set up. Based on limited number of patients with mammary  dysplasia, a number of trials suggested that the risk of breast cancer  may be reduced by vitamin E supplementation 

. Larger trials on benign breast disease, however, failed to confirm these results 

Vitamin E supplement was shown to reduce prostate cancer incidence and mortality by one-third in men who smoke 

. The simultaneous addition of lycopen together with  alpha-tochopherol resulted in a strong inhibitory effect of prostate  carcinoma cell proliferation

. Also oral administration of  alpha-tochopherol resulted in both clinical and histopathological  responses in oral premalignant leukoplakia lesions 

In the present study, the group received local injection  of vitamin E showed significantly complete response rates in a  significantly shorter duration than the control group, although serum  vitamin E levels were consistently low in both groups.

Patients received oral vitamin E supplementation showed  no significant response compared to the placebo group, although serum  vitamin E levels were significantly higher in patients receiving vitamin  E than in patients receiving placebo after 6 months of supplementation.

This could be explained by the possibility that the  amount of vitamin E that accumulated in the cervix may not be high  enough when administered orally for a short period. It is also possible  that the timing of the dose may affect the results.

In the present study it was observed that small lesions  <100mm2 responded significantly than larger lesions >100mm2, which  indicates that tissue levels of vitamin E is more important than serum  levels in predicting the response rate.
 
 


 
 Vitamin E injected into the lesion in cases with CIN give significant  response rates, and smaller lesions tend to respond more significantly  than larger lesions.
 Further studies with larger and more frequent local doses of with measuring tissue levels of vitamin E is recommended. 

Table II: Colposcopic findings in all groups

Table III: Response rate among all groups

Table V: Relation between size of lesion and response rate in patients treated by vitamin E (group I & III)

Table VI: Serum vitamin E levels at the start and after  6 months of study

1-National Institute of Health,Consensus Development Conference Statement: Cervical Cancer. NIH Census Statement 1996 April,1-3;14(1):1-38.

2-Birt DF . Update on the effects of vitamins A,C and E and selenium on carcinogenesis. Proc.Soc.Exp.Biol.Med.,1986,183:311-320(abstr.)

3-Chen LH; Biossonneault GA; and Glauert HP. Vitamin C, Vitamin E and cancer . Anticancer Res.,1988,8:739-748 (review).

Vitamin E (alpha-tocopherol) is thought to play a role in several stages of carcinogenesis through its contribution to immunocomptence, inhibition of mutation formation and repair of membranes and DNA.

Author | Samir Fouad Abdel Aziz, MD

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