Greece’s economic recession hits her youngest citizens: Children abandoned in hospitals

Iliodromiti Zoe1, Vlachadis Nikolaos1, Vlachadi Maria2, Kalantaridou Sofia3, Vrachnis Nikolaos1

12nd Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens, School of Medicine, Aretaieio hospital, Athens, Greece

2 Department of Political Sciences, University of Crete, Rethymno, Greece

3 Department of Obstetrics and Gynecology, University of Ioannina, School of Medicine, Ioannina, Greece

Correspondence: Vlachadis Nikolaos, 2nd Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens, School of Medicine, Aretaieio hospital, 76 Vasilissis Sofias Avenue, GR-11528, Athens, Greece. E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Key words: abandoned children; economic crisis; Greece

 


 

Ιn the end of 2008, Greece entered the country’s deepest recession in peacetime history, with the unemployment rate increasing from 7.9% to 26.0% from the fourth trimester of 2008 to the fourth trimester of 2012. By 2012, Greece had the highest at - risk - of - poverty rate (23.1%) among the 28 countries of the European Union1.

In this suffocating economic climate, births decreased substantially in Greece especially among the most vulnerable social groups2. However, even for people who are impoverished a birth of a child usually turns to a daily struggle even to cover the basic needs.

In an economically battered Greece, as parents run out of the means to care for their offspring, a growing number of children are being abandoned in maternity hospitals by their mothers soon after labor or are left in large children’s hospitals. No official data are available, but agencies and charity organizations have reported that approximately 1,200 children were abandoned in Greece during 2011 alone, which is the highest value among the countries of Southern Europe struggling with austerity3.

According to the only official data recently presented by the health minister in the Hellenic Parliament, the number of children who were dispatched under court order to the Athens “P & A Kyriakou” children’s hospital increased from 42 in 2010 to 96 in 2011 and 130 in 2012, a 3fold rise between 2010-2012. During the first ten months of 2013 the situation remained distressing, with the number at 102 children4.

These children are of Hellenic or foreign citizenship and of different ages who were abandoned by parents unable to financially support them. Some of them are also abused and neglected. Most of the children were born out of wedlock, and some of them to parents afflicted by serious social and psychological problems.

However, the financial recession is only a part of the story. Another aggravating issue is the malfunctioned and antiquated legislation for adoption in Greece since it has not been brought into line with European norms. Meanwhile, the concept of foster care is not yet widely accepted.

The effects of austerity are becoming devastating for Greece’s youngest citizens. Newborns and young children grow up in overburdened public hospitals in the same departments with patients suffering from various health issues, exposed to obvious risks to their health and social and psychokinetic development5. There is an urgent need to take measures immediately in order to support poverty-stricken families with young children, ensure that children will be removed from hospital wards and also, develop strategies aimed at reintegrating these children into their own families or enabling them to enter a foster home.

 

Conflict of interest

All authors declare no conflict of interest

 

 

References

  1. http://appsso.eurostat.ec.europa.eu/nui/show.do?dataset=ilc_li02&lang=en
  2. Vrachnis N, Vlachadis N, Iliodromiti Z, Vlachadi M, Creatsas G. Greece’s birth rates and the economic crisis. Lancet 2014;383:692 - 3. PubMed
  3. The Daily Beast. http://www.thedailybeast.com/articles/2012/07/11/europe-s-growing-crisis-of-abandoned-babies.html
  4. http://www.tovima.gr/society/article/?aid=558875
  5. Giordano S. Crimes and misdemeanours: the case of child abandonment. J Med Ethics 2007;33:28 - 34. PubMed

Imperforate hymen with hematocolpometra: A new diagnostic approach using 2D and 3D translabial ultrasonography

Zacharakis Dimitrios, Domali Ekaterini, Antsaklis Panos, Daskalakis George

First Department of Obstetrics and Gynecology, University of Athens, Alexandra hospital, Athens, Greece

Correspondence: Daskalakis George, 8 Metaxa St & 1 Vasilissis Sofias St, P. Penteli, GR-15236, Athens, Greece. E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.


 

Abstract

Imperforate hymen is a urogenital tract anomaly that represents the most frequent congenital malformation of the female genital tract. We present a case of a young girl who was referred to our pediatric and adolescent gynecological department with a transabdominal ultrasound showing a suspicious pelvic mass. Using translabial ultrasonography the diagnosis of imperforate hymen was confirmed. Translabial ultrasound scan provides an excellent alternative to the transvaginal technique where vaginal access is impossible. Furthermore, allows differentiating imperforate hymen from low transverse vaginal septum, thus helping clinicians in tailoring management options.

Key words: abdominal pain; hematocolpometra; imperforate hymen; pelvic mass; translabial ultrasonography

 

Ιmperforate hymen is the most common congenital malformation of the female genital tract. It represents a sporadic condition with an incidence that ranges between 0.014 and 0.1% at term1. Diagnosis of imperforate hymen is usually based on the characteristic symptoms of cyclical pain, primary amenorrhea and palpable pelvic mass combined with clinical examination and imaging studies. Transabdominal ultrasonography (USG) is the commonest imaging method used for the diagnosis of the anomaly2-5. However, there are cases that can be misleading6. In addition, transabdominal USG cannot always identify other coexisting congenital anomalies of the lower genital tract. Thus, other imaging modalities are commonly used in order to confirm the diagnosis2-4.

 

Case report

An 11 years old girl was referred to our pediatric and adolescent gynecology department with a provisional diagnosis of an ovarian tumor upon a finding of a pelvic mass on transabdominal ultrasonography (USG) (Figure 1). She was complaining of pelvic distension, cyclic abdominal pain, disturbance of the defecation and urinary hesitancy. Symptoms had started 6 months before, but significantly worsened over the last seven days. No clinical examination was attempted due to severe pain and discomfort. Her past medical history was unremarkable, and no medications were assumed. She also denied trauma, fall or sexual abuse. Although breast development, axillary and pubic hairs were at Tanner stage 3, she had not experienced menarche. Examination of the perineum revealed an imperforate hymen, which was vascular, bluish, and was completely obstructing the vagina, while on abdominal examination a palpable mass was felt. A pelvic mass of 142 x 87mm that was occupying entirely the vagina was revealed (Figure 2). The mass was filled with hemorrhagic fluid. By using the least pressure possible to the transducer fluid movement was observed. This technique allows excluding the presence of a lower vaginal septum that may present with similar clinical symptoms. In addition, sagittal 3D translabial USG confirmed the absence of a lower transverse or longitudinal fibromuscolar septum (Figure 3).

The patient was treated with stellate incisions through the hymenal membrane and excision of the individual segments, under general anesthesia. Finger pressure to the vaginal canal from the rectum accomplished drainage of accumulated menses. Approximately 500cc of dark, red blood was drained. Postoperative period was uneventful and the patient was discharged the day after. On 12 weeks postoperative follow-up she reported a regular menstrual pattern without any difficulties in urination or defecation.

 

 dask 1

Figure 1: Transabdominal evaluation of hematocolpometra

 

dask 2

Figure 2: 2D translabial sonography imaging hematocolpos and absence of a lower vaginal septum

 

dask 3

Figure 3: 3D translabial sonography at the level of the introitus showing vagina filled with hemorrhagic fluid (middle arrow).

Upper arrow indicates the level of the symphysis pubis and lower arrow shows the anal sphincter

 

Discussion

In the embryological period, the lateral portion of the hymen originates from a fold of the urogenital sinus. The posterior part originates from the cells of the urogenital sinus, externally, and from Müller’s duct, internally. Usually, at the 8th week of gestation, it partially ruptures in the inferior part of Müller’s duct, remaining as a fold of mucous membrane around the entrance of the vagina. Failure of these events results in persistence of the septum7.

Imperforate hymen is rarely diagnosed in the neonatal period, and most cases are presented to the gynecologist between the age of 11 and 15. Cyclical pelvic pain 2.5 to 4 years after thelarche, primary amenorrhea and a palpable pelvic mass represent the characteristic clinical symptomatology8. Urological problems related to external compression of the bladder and ureter are also very common. Urinary hesitancy and dysuria are detected in as many as 58% of patients with hematocolpos9.

Although clinical examination is in most cases sufficient for the diagnosis of imperforate hymen, imaging studies are also necessary to confirm the presence of hematocolpos or hematometra. Transabdominal USG is the commonest method used for that purpose2-5. However, in some occasions findings can be misinterpreted as a suspicious pelvic mass and provoke severe anxiety to a young girl and her family. In addition, to further clarify spurious findings of transabdominal USG and rule out possible associated congenital anomalies, other imaging or invasive modalities have been used such as CT scan, MRI scan and videolaparoscopy2-4. All of them are very accurate in diagnosis of hematocolpos and hematometra, however, they are not considered to be cost-effective2-4.

Transrectal USG has also been reported as a method of evaluating pelvic anatomy in young girls with no sexual activity5. Although, it has been quite accurate in diagnosis of hematocolpos, it is not considered to be an acceptable method for this age group, due to possible psychological implications.

According to our knowledge, this is the first case where translabial USG has been used for the diagnosis of imperforate hymen causing hematocolpometra. Translabial USG provides an excellent alternative to transvaginal technique, in cases where vaginal access is not amenable. The method is both efficient and feasible and has become an individual technique for examining the uterus, adnexa, vagina and other non gynaecologic structures in the pelvis, as it provides a better spatial resolution than transabdominal USG10. Although transabdominal scanning is useful to determine if hematocolpos or hematocolpometra is present, this method does not allow visualization of a caudally placed obstructive septum. In contrast, translabial USG due to its proximity to the pelvic organs and especially to the vagina allows a dynamic examination of these structures10. This technique is suitable for differentiating imperforate hymen from low transverse vaginal septum by visualizing the movement of the hemorrhagic fluid in contact with the hymen. Accurate preoperative diagnosis is important for optimal planning of treatment. A caudal vaginal septum requires quantification of the obstructive segment followed by a carefully planned vaginal reconstructive procedure.

The possibility of hematocolpometra should always be suspected when evaluating adolescent girls with a pelvic mass, low intermittent abdominal pain, and urinary difficulties. Ultrasound imaging has an established role in the assessment of these symptoms. We propose a different, non invasive, but accurate approach of evaluation. Translabial ultrasound imaging may become a diagnostic standard with imperforate hymen presenting to pediatric and adolescent gynecologists due to ease of use, availability of equipment and patient’s acceptance.

 

Conflict of interest

All authors declare no conflict of interest.

 

References

  1. Messina M, Severi FM, Bocchi C, Ferrucci E, Di Maggio G, Petraglia F. Voluminous perinatal pelvic mass: a case of congenital hydrometrocolpos. J Matern Fetal Neonatal Med 2004;15:135 – 7. PubMed
  2. Deligeoroglou E, Deliveliotou A, Makrakis E, Creatsas G. Concurrent imperforate hymen, transverse vaginal septum, and unicornuate uterus: a case report. J Pediatr Surg 2007;42:1446 - 8. PubMed
  3. Partsinevelos GA, Rodolakis A, Loutradis D, Antsaklis A. Imperforate hymen is associated with elevated serum CA125 and CA19-9 levels: a reappraisal. J Obstet Gynaecol 2009;29:560 - 1. PubMed
  4. Hsu KP, Chen CP, Chien SC, Hsu CY. Hematocolpometra associated with an imperforate hymen and acute urinary retention mimicking a pelvic mass. Taiwan J Obstet Gynecol 2008; 47:222 - 3. PubMed
  5. Kushnir O, Garde K, Blankstein J. Rectal sonography for diagnosing hematocolpometra. A case report. J Reprod Med 1997;42:519 - 20. PubMed
  6. Posner JC, Spandorfer PR. Early detection of imperforate hymen prevents morbidity from delays in diagnosis. Pediatrics 2005;115:1008 - 12. PubMed
  7. Langman’s Medical embryology. Baltimore: Williams and Wilkins; 1998, p. 296.
  8. Adaletli I, Ozer H, Kurugoglu S, Emir H, Madazli R. Congenital imperforate hymen with hydrocolpos diagnosed using prenatal MRI. AJR Am J Roentgenol 2007;189:23 -5. PubMed
  9. Chircop R. A case of retention of urine and haematocolpometra. Eur J Emerg Med 2003;10:244 - 5. PubMed
  10. Shek KL, Dietz HP. Pelvic floor ultrasonography: an update. Minerva Ginecol 2013;65:1 - 20. PubMed

Gestational diabetes: Its classification and optimal management

Vitoratos Nikolaos, Vrachnis Nikolaos, Vlahos Nikolaos, Peristeris Kostantinos, Iliodromiti Zoe, Creatsas George

2nd Department of Obstetrics and Gynecology, University of Athens, Medical School, Athens, Greece

Correspondence: Vrachnis Nikolaos

2nd Department of Obstetrics and Gynecology, Aretaieio hospital, University of Athens, Medical School,124B Vasilissis Sofias Avenue, GR-11526, Athens, Greece. 

E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. 

 


 

Abstract

The classification of diabetes mellitus includes diabetes mellitus type I, diabetes mellitus type II, gestational diabetes and other specific types. Unfortunately, the incidence diabetes mellitus in pregnancy, or gestational diabetes, today ranging between 4 and 7%, has been globally on the rise in recent years, particularly among women over 32 years old. According to the International Association of the Diabetes and Pregnancy Study Groups (IADPSG), a pregnant woman can be at low, average or high risk of developing diabetes during pregnancy. A new strategy for the diagnosis of gestational diabetes has been proposed, focusing on the measurement of fasting glucose plasma level to be performed during the 1st trimester of pregnancy. The management of women with gestational diabetes entails: a) treatment of the women, b) antepartum surveillance tests, c) appropriate timing and mode of delivery, d) postpartum follow-up. Management also includes monitoring after the birth, since the likelihood of developing Diabetes type II is 7 times greater in women with a history of gestational and the recurrence rate of gestational diabetes during a subsequent pregnancy is approximately 40%.

Key words: gestational diabetes; diabetes mellitus; pregnancy; management; follow-up; classification

 

 

 

The incidence of diabetes on a global scale has increased dramatically in recent years, with the biggest rise being recorded in ages over 65 years old, while a considerable increase is also seen in younger people up to the age of 44 years1. The prevalence of all the types of diabetes mellitus (DM) during pregnancy (DM type I, DM type II and gestational diabetes) ranges from 4 to 7%. The largest percentage, approximately 88%, concerns diabetes appearing for the first time in the mother or diabetes diagnosed for the 1st time in pregnancy2.This type of diabetes has markedly increased in recent years, according to recent diagnostic criteria3. This is mainly due to the increase of the mean age of reproduction as well as the ever rising percentage of overweight/obese women getting pregnant.

Today it is well established that the blood sugar levels in a pregnant woman are directly proportional to the perinatal and maternal outcome. Recent studies in a large number of pregnancies showed that the higher the mother’s blood sugar level (though not exceeding the normal physiological values), the higher the frequency of babies born above the 90th growth percentile, cesarean section, incidence of neonatal hypoglycemia and increased levels of C-peptine in the umbilical blood4-6.

 

tab1

 

Classification of diabetes mellitus in pregnancy

A pregnant woman with disorders in homeostasis of glucose and subsequent hyperglycemia could develop one of the following types of diabetes:

Diabetes mellitus type I. Destruction of pancreatic β-cells in these women is characteristic. These women are younger than 30 years of age and usually have a family history of autoimmune diseases.

Diabetes mellitus type II. Usually in obese women of 30 years of age or older diagnosed with inadequate insulin secretion or increased tissue resistance to insulin.

Gestational diabetes. This concerns diabetes appearing for the first time in the patient or diabetes diagnosed for the 1st time in pregnancy.

Diabetes associated with the incidence of an endocrinopathy, such as Cushing’s syndrome or suprarenal glands hyperplasia, or due to drugs administration, such as corticosteroids, or due to exposure to toxic substances7. Every pregnant woman has a 2-17% risk (mean: 7%) of developing diabetes mellitus during pregnancy⁸. The term gestational diabetes concerns a heterogeneous group of women. It is not certain which women will need diet adaptation alone or a strict diet combined with insulin treatment or an oral antidiabetic tablet regimen. Furthermore, this term does not precisely define the severity of the disease (Table 1)8.

According to the International Association of the Diabetes and Pregnancy Study Groups (IADPSG), a woman can have a very low, high or intermediate risk of developing diabetes during pregnancy. Low-risk comprises women who belong to an ethnicity of low DM type II incidence, are aged 25 or younger, have a normal BMI before the pregnancy, do not show a complicated obstetric history and do not have a history of hyperglycemia of any kind. These women are in no need of testing for gestational diabetes via the fasting glucose tolerance test method (Table 2).

 

tab2

 

By contrast, high-risk includes women who have a history of gestational diabetes or of a pathological curve in their glucose tolerance test or increased levels of pre-meal glucose. Furthermore, they have a complicated obstetric history (intrauterine death, congenital fetal anomalies, miscarriages, births of neonates exceeding 4,500gr), are aged over 35 years and present with vascular lesions, symptoms of glycosuria and/or a family history of DM type II (Table 3)8,9.

These women should be checked via a glucose curve at their first consultation at the start of pregnancy. A timely glucose tolerance test will thereby uncover women with DM type II. It is moreover well known that DM II is responsible for congenital anomalies in the embryo at almost the same frequency as DM type I10.

The rest of the female population belongs to the intermediate-risk group and these women should undergo a glucose tolerance test between the 24th – 28th weeks of gestation.

A new strategy for the diagnosis of diabetes in pregnancy has been proposed. It involves measurement of the morning fasting glucose levels of the pregnant woman after the 1st visit. If the glucose levels are less than 92mg/dL, the woman will undergo a glucose tolerance test between the 24th – 28th weeks of gestation11,12. If the glucose levels are found to be more than 126mg/dL, then the woman is definitely suffering from diabetes mellitus and should be monitored and treated as in the case of pre-existing diabetes mellitus in pregnancy. If the results are not diagnostic for diabetes mellitus type II and the glucose fasting plasma level is more than 92mg/dL, but less than 126mg/dL, then a diagnosis of gestational diabetes is almost certain (Table 3)11,12.

The glucose tolerance test is carried out by administering 75gr of glucose. Prior to glucose administration, a blood sample is obtained, which reflects the fasting glucose level (time 0’). The blood sugar level measurement then follows at 1 hour and 2 hours after the glucose administration. The physiological range is up to 92mg/dL for the fasting glucose level (time 0’), up to 180mg/dL for the 1st hour measurement and up to 153mg/dL for the 2nd hour. In the event that one of the above measurements exceeds the cut-off point, the diagnosis of gestational diabetes is established12.

 

Management of gestational diabetes

A basic question is if the therapy has a beneficial effect on the perinatal outcome, to which a recent systematic review and meta-analysis has provided a clear answer. It was found that upon completion of the therapy, perinatal and neonatal mortality decreased. Fewer macrosomic children were born, while the incidence of neonatal hypoglycemia, trauma during labor and the need for intensive care of neonates dramatically decreased13.

The general management of women with diabetes mellitus in pregnancy entails the conservation of physiological glucose levels in the mother’s blood. In this endeavor, diet, exercise, insulin or antidiabetic pill administration and the daily monitoring of glucose levels play a crucial role. Furthermore, the management includes strict overall observation of the pregnant woman and the endometrial wellbeing of the fetus, the appropriate time and mode of delivery and, of course, the management of the mother after delivery (Table 4)14.

 

tab3-4

 

The role of diet

Concerning diet, the majority of women should receive a dietary program in which calorie intake does not exceed 2,000 - 2,500 daily. The carbohydrate calorie intake should be limited to 33 - 40% of the total calorie requirements and should be preferably synthetic carbohydrates. On the other hand, low saturated fatty acids should cover less than 7% of the calorie requirements15. The American Diabetes Association recommends that women of BMI> 30 should limit their calorie intake by 30 - 33% during pregnancy16.   However, the daily intake should not be lower than 1,50017,18. The maternal and neonatal outcome is strongly dependent on the recommended weight that the mother needs to attain during the pregnancy, while they also depend on the BMI of the woman before the pregnancy. The weight increase has to be minimal during the 1st trimester (0.5 - 2kg) to ensure that changes in the embryo and the maternal tissues are small. Meanwhile, during the 2nd and 3rd trimester, the weekly weight increase should be 0.35 - 0.50kg. Overweight women (BMI 26 - 29) should not increase their weight by more than 7 - 11.5kg, whereas obese women with BMI over 30 should gain no more than 5 - 9kg19,20.

 

The effect of exercise

Mild exercise or walking for approximately 20 minutes daily helps with the improvement of glucose regulation in the female and her general wellbeing21.

 

Daily monitoring of glucose levels

This daily monitoring is of the utmost importance for women with gestational diabetes. Usually it is recommended to have 4 measurements per day (measurement of fasting glucose in the morning and 3 ensuing measurements, once after each meal)22,23. Some prefer to check the glucose levels 1 hour after meals or even 2 hours later. However, this slight difference in measurements does not affect the perinatal outcome23. The objective is to keep the woman’s glucose fasting levels between 60 - 90mg/dL by means of a controlled diet and daily exercise. Furthermore, it is required that the glucose levels do not exceed 140mg/dL 1 hour after a meal and also that they do not exceed 120mg/dL 2 hours after a meal24,25.

 

The role of insulin

If the desired glucose levels before and after meals are not achieved by means of lifestyle changes, then the administration of insulin is deemed necessary. The quantity and type of insulin depends on the pre-meal and post - meal glucose levels. Insulin is also recommended for women who, even though successfully not exceeding the physiological upper glucose levels, have fetuses showing, in an ultrasound scan at 32 weeks of gestation, an abdominal circumference higher than the 75th percentile. The same applies to women who, despite their physiological glucose levels, exhibit hydramnios26.

 

Antidiabetic tablets

Researchers have recently embraced the use of antidiabetic tablets orally for the control of hyperglycemia in women with gestational diabetes. The most commonly used is metformin. In a comparative study between 363 women who tried metformin and 370 who tried insulin, no substantial difference was found in the perinatal outcome27. A large clinical study also concludes that metformin is a safe and effective treatment, alternative to insulin treatment in women with gestational diabetes, without any adverse effects on the maternal or perinatal outcome28. Nevertheless, some researchers are skeptical regarding this new alternative treatment, since it has been observed that 46% of women who took metformin needed either additional insulin or exclusively insulin for the successful management and regulation of glucose8.

 

Monitoring of the pregnancy and the wellbeing of the fetus

As in all pregnancies, a measurement of the Crown-Rump Length of the fetus should be carried out for the exact determination of its age and vitality. The measurement of nuchal translucency should be carried out between the 11th and 14th week for the detection of possible chromosomal abnormalities in the embryo. The fetal anatomy ultrasound scan should be carried out between the 20th and 22nd week. Furthermore, a monthly ultrasound check is strongly advised for monitoring of fetal wellbeing and growth as well as for the evaluation of amniotic fluid. An ultrasound scan should be also performed in the 38th week of gestation. The endometrial assessment of the fetus is completed with the NST test or with the biophysical profile. In women with good glucose control via diet alone and who do not show complications, the aforementioned tests may not be necessary on a monthly basis. They are, however, mandatory and should be done in between 32 to 34 weeks. Particularly in women with complications, as well as in those who take insulin, scans should be done twice per week7,29.

 

Appropriate timing and mode of delivery

There are many protocols concerning the time and mode of delivery in women with gestational diabetes. The American Diabetic Association suggests that the delivery be carried out during the 38th week, unless the obstetric parameters indicate delivery should be induced sooner29.According to the American College of Obstetricians and Gynecologists, the time of delivery is always under discussion. If there are no complications present, no signs of fetal distress and the glucose levels are satisfactory, the delivery may take place at the 40th week of gestation. Cesarean section is preferred in cases where the baby’s weight is estimated to be larger than 4,500gr30. According to the National Institute for Health of the United Kingdom, delivery either by cesarean section or vaginally should occur after the 38th week. That being said, glucose levels should be constantly monitored during the pregnancy so that they are maintained between 73 - 126mg/dL (4 - 7mmol/L) for the full duration of the pregnancy30.

 

Postpartum observations

After delivery, the mother does not need particular regulation of glucose levels. She should, however, be submitted to a glucose tolerance test. The trial is done with 75gr of glucose 6 - 12 weeks after labor. The purpose of this test is to identify women with clinical diabetes mellitus or with a pathological glucose curve31. Women diagnosed with clinical diabetes should be referred to a diabetic clinic. According to the American Diabetes Association, women with normal results from the glucose tolerance test should be screened every 3 years and those with pathological results yearly30.The same approach is proposed by the American College of Obstetricians and Gynecologists, with the addition of the administration of metformin to blood glucose fasting levels between 120 - 126mg/dL, as well as in women with a pathological glucose curve30,31.

 

Future risk

The risk of developing gestational diabetes is approximately 41% for women with a history of the disease by contrast to only about 4% for those women with no previous diagnosis of it. The probability of developing diabetes is even greater in the 3rd pregnancy of women who showed signs of the disease in their previous two pregnancies (Table 4)32,33.

The risk of developing diabetes mellitus type II, as shown by a recent systematic review and meta-analysis of 643,588 patients, is 7 times greater in those who showed signs of gestational diabetes compared to those who didn’t34. In another study involving observation of 11,270 women with a history of gestational diabetes over a span of 10 years and 185,416 women with a history of normal uncomplicated pregnancy, it was shown that in this time span 15.7% of the women of the 1st category and only 1% of those of the 2nd were diagnosed with diabetes mellitus type II35.

 

Conflict of interest

All authors declare no conflict of interest.

 

 

References

  1. Prevalence of Diabetes-Center for Disease Control and Prevention. www.cdc.gov/diabetes/statistics/prev/national/figbyage.htm
  2. Wier LM, Witt E, Burgess J, Elixhauser A. Healthcare cost and utilization project. Agency for health care policy and research. 2010.
  3. Negrato CA, Mattar R, Gomes MB. Adverse pregnancy outcomes in women with Diabetes. Diabetol Metab Syndr 2012;4:41. PubMed
  4. Metzger BE, Lowe LP, Dyer AR, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008;358:1991 - 2002. PubMed
  5. Hapo Study Cooperative Research Group. Hyperglycemia and adverse pregnancy outcome (HAPO) study: associations with neonatal anthropometrics. Diabetes 2009;58:453 - 9. PubMed
  6. Kautzky-Willer A, Bancher-Todesca D, Pollak A, Repa A, Lechleitner M, Weitgasser R. Gestational diabetes mellitus. Wien Klin Wochenschr 2012;124 Suppl 2:58 - 65. PubMed
  7. Metzger BE, Gabbe SG, Persson B. et al. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010;33:676 - 82. PubMed
  8. Landon MB, Gabbe SG. Gestational diabetes mellitus. Obstet Gynecol 2011;118:1379 - 93. PubMed
  9. Falavigna M, Prestes I, Schmidt MI, Duncan BB, Colagiuri S, Roglic G. Impact of gestational diabetes mellitus screening strategies on perinatal outcomes: a simulation study. Diabetes Res Clin Pract 2013;99:358 - 65. PubMed
  10. Murphy HR, Steel SA, Roland JM, et al. Obstetric and perinatal outcomes in pregnancies complicated by type 1 and type 2 diabetes: influences of glycaemic control, obesity and social disadvantage. Diabet Med 2011;28:1060 - 7. PubMed
  11. Lehmann R, Troendle A, Brandle M. New insights into diagnosis and management of gestational diabetes mellitus: recommendations of the Swiss Society for Endocrinology and Diabetes. Ther Umsch 2009;66:695 - 706. PubMed
  12. Wendland EM, Torloni MR, Falavigna M, et al. Gestational diabetes and pregnancy outcomes - a systematic review of the World Health Organization (WHO) and the International Association of Diabetes in Pregnancy Study Groups (IADPSG) diagnostic criteria. BMC Pregnancy Childbirth 2012;12:23. PubMed
  13. Vamberque A. Gestational diabetes: diagnosis, short and long term management. Presse Med 2013;42:893 - 9. PubMed
  14. Horvath K, Koch K, Jeitler K, et al. Effects of treatment in women with gestational diabetes mellitus: systematic review and meta-analysis. BMJ 2010;340:c1395. PubMed
  15. Roussell MA, Hill AM, Gaugler TL, et al. Beef in an optimal lean diet study: effects on lipids, lipoproteins, and apolipoproteins. Am J Clin Nutr 2012;95:9 - 16. PubMed
  16. American Diabetes Association. Medical management of pregnancy complicated by diabetes. Nutritional management during pregnancy in preexisting diabetes. 3rd edition. Alexandria, Virginia: ADA, 2000, p. 70 - 86.
  17. Dornhorst A, Nicholls JSD, Probst F, et al. Calorie restriction for treatment of gestational diabetes. Diabetes 1991;40:161-4. PubMed
  18. Jacqueminet S, Jannot-Lamotte MF. Therapeutic management of gestational diabetes. Diabetes Metab 2010;36:658 - 71. PubMed
  19. Cedergren MI. Optimal gestational weight gain for body mass index categories. Obstet Gynecol 2007;110:759 - 64. PubMed
  20. Crane JM, White J, Murphy P, Burrage L, Hutchens D. The effect of gestational weight gain by body mass index on maternal and neonatal outcomes. J Obstet Gynaecol Can 2009;31:28 - 35. PubMed
  21. Avery MD, Leon AS, Kopher RA. Effects on particularly home-based exercise program for women with gestational diabetes. Obstet Gynecol 1997;89:10 - 5. PubMed
  22. Crowther CA, Hiller JE, Moss JR, et al. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005;352:2477 - 86. PubMed
  23. Landon MB, Spong CY, Thom E, et al. A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med 2009; 361:1339 - 48. PubMed
  24. Metzger BE, Buchanan TA, Coustan DR, et al. Summary and recommendations of the fifth international workshop-conference on Gestational Diabetes Mellitus. Diabetes Care 2007;30 Suppl 2:S251 - 60. PubMed
  25. Langer O, Rodriguez DA, Xenakis EM, McFarland MB, Berkus MD, Arrendondo F. Intensified versus conventional management of gestational diabetes. Am J Obstet Gynecol 1994;170:1036 - 46. PubMed
  26. Kjos SL, Schaefer-Graf U, Sardesi S, et al. A randomized controlled trial using glycemia plus fetal ultrasound parameter versus glycemic parameters to determine insulin therapy in gestational diabetes with fasting hyperglycemia. Diabetes Care 2001;24:1904 - 10. PubMed
  27. Rowan JA, Hague WM, Gao W, et al. Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med 2008;358:2003 - 15. PubMed
  28. Niromanesh S, Alavi A, Sharbaf FR, Amjadi N, Moosavi S, Akbari S. Metformin compared with insulin in the management of gestational diabetes mellitus: a randomized clinical trial. Diabetes Res Clin Pract 2012;98:422 - 9. PubMed
  29. Landon MB, Gabbe SG. Antepartum fetal surveillance in gestational diabetes mellitus. Diabetes 1985;34:50 - 54. PubMed
  30. Simmons D, McElduff A, McIntyre HD, et al. Gestational diabetes mellitus: NICE for the U.S.? A comparison of the American Diabetes Association and the American College of Obstetricians and Gynecologists Guidelines with the U.K. National Institute for Health and clinical excellence guidelines. Diabetes Care 2010;33:34 - 37. PubMed
  31. Committee on Obstetric Practice. ACOG Committee Opinion No.4335: postpartum screening for abnormal glucose tolerance in women who had gestational diabetes mellitus. Obstet Gynecol 2009;113:1419 - 21. PubMed
  32. Getahun D, Fassett MJ, Jacobsen SJ. Gestational diabetes: risk of recurrence in subsequent pregnancies. Am J Obstet Gynecol 2010;203:467.e1-6. PubMed
  33. Russell C, Dodds L, Armson BA, Kephart G, Joseph KS. Diabetes mellitus following gestational diabetes: role of subsequent pregnancy. BJOG 2008;115:253 - 259. PubMed
  34. Bellamy L, Casas JP, Hingorani AD, Williams D. Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet 2009;373:1773 - 9. PubMed
  35. Chodick G, Elchalal U, Sella T, et al. The risk of overt diabetes mellitus among women with gestational diabetes: a population-based study. Diabet Med 2010;27:779-85. PubMed

Uterine prolapse complicating pregnancy: A case report

Ammari Alexandros1, Tsikouras Panagiotis1, Dimitraki Marina1, Liberis Anastasios1, Kontomanolis Emmanuel1, Galazios Georgios1, Liberis Vasileios1

1Department of Obstetrics and Gynecology, School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece

Correspondence: Tsikouras Panagiotis, Department of Obstetrics and Gynecology, Democritus University of Thrace, School of Medicine, Alexandroupolis, Greece.

E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.


 

Abstract

Uterine prolapse concurrent with pregnancy is a rare event. Complications resulting from the prolapse of the uterus in pregnancy vary from minor cervical infection to spontaneous abortion, preterm labor and maternal and fetal death. We report a case of stage 3 uterine prolapse during pregnancy presented at our antenatal clinic. The patient had pre-existing uterine prolapse, was treated conservatively with bed rest and the use of a pessary and had a successful vaginal delivery at 39 weeks of gestation. Conservative treatment of these patients throughout pregnancy can result in an uneventful, normal, spontaneous delivery.

Key words: uterine prolapse; pregnancy; management

 

 

Uterine prolapse is the protrusion of the cervix and uterus towards the introitus due to poor cardinal and uterosacral ligament apical support1. The prevalence of any degree of prolapse in women presenting for routine gynaecological care with loss of vaginal or uterine support, ranges from 30-38%, while 2 - 6% of the population have prolapse beyond the hymen (stage 3)2. Uterine prolapse during pregnancy is undoubtedly a rare condition with estimated incidence between 1 in 10,000 and 15,000. This incidence rate has decreased during the past decade, especially in developed countries, mainly due to the gradual decrease in parity3.

 

 

uterine a

uterine b

Figure 1, 2. Uterine cervical prolapse in pregnant woman with noticeable cervical edema and inflammation

 

Case report

A 32 year old, gravida 2, woman presented to the obstetrics outpatient clinic at 8 weeks gestation (Figure 1, 2). The patient had a known history of cervical prolapse during the past three years and according to Pelvic Organ Prolapse Quantification (POPQ) system the prolapse was classified as Stage 3 (more than 1 cm below the plane of the hymen but protrudes no further than 2cm less than the total length of the vagina). She was fitted with a donut pessary for uterine support.

Her obstetric history included a vacuum-assisted vaginal delivery at 29 years of age at 39 weeks gestation. Duration of labor was considered normal with the first stage of labor lasting 7 hours and the second stage 45 minutes. She delivered a 3420gr male infant with Apgar scores of 9 and 10 at minutes 1 and 5, respectively.

With removal of the pessary the prolapse was apparent but easily reduced. She was advised to continue pessary support with regular removal and cleaning of the pessary. No complications were observed while the pregnancy progressed to term. She presented at 39 weeks gestation with spontaneous labor. The cervix was at the level of the introitus, 4cm dilated, with intact membranes. After approximately six hours of uneventful labor, she delivered a 2,980gr female infant with Apgar scores of 9 and 10 at minutes 1 and 5, respectively.

 

Discussion

The first known writings on uterine prolapse were found in the Ebers Papyrus of about 1550 BC. Hippocrates (ca. 460-370 BC) referred to uterine prolapse extensively in his writings and he even proposed a number of treatments among which was a vaginal pessary in the form of a half pomegranate soaked in wine and being introduced into the vagina following the successful reduction of the prolapse with a cold wine impregnated sponge4.

Uterine prolapse during pregnancy is a rare condition, occurring during the pregnancy or pre-existing. Many etiological factors may contribute to the development of the disorder. Multiparity, vaginal delivery, advanced maternal age and increased body mass index are the most usual causative factors. White and Hispanic women have a higher incidence of uterine prolapse compared to those of African and Asian descent. This could be due to genetic racial differences in pelvic structure and the strength of supporting pelvic muscles and connective tissue. The strong familial incidence of genital prolapse is proved by the fact that it occurs equally in identical twins given the same conditions of stress. Pelvic surgery (e.g. colposuspension), pregnancy, especially at young age, previous childbirth with medical intervention, with prolonged second stage of labor or delivery of a macrosomic neonate, have been associated with higher rates of uterine prolapse. Moreover, contributing factors are situtations that lead to raised intra-abdominal pressure, including straining, constipation, heavy lifting and chronic obstructive airway disease4-9.

Pre-existing prolapse is associated with infertility, spontaneous abortions and preterm labor. Spontaneous abortion rate is reported of up to 15%. Cervical edema is due to venous obstruction and stasis whereas the edematous protruding cervix is susceptible to mechanical trauma which could lead to ulceration and infection. Urinary tract infection and acute urinary retention have also been reported as complications of uterine prolapse during pregnancy9-11.

The main intrapartum complications include inability of cervical dilatation, cervical laceration and obstructive labor. Inability or resistance of cervical dilatation is due to the fact that the process is initiated outside the introitus while the edema of the cervix adds strain to its fibrous nature and may lead to cervical dystocia. Uterine rupture at the lower segment of the uterus has also been reported12,13.

In the early 20th century puerperal infections were more common with a mortality rate reaching 5% in gravidas with uterine prolapse. However, the last reported maternal death, as a result of sepsis, was in 19251. Uterine prolapse may persist or even be exacerbated by pregnancy due to the physiological increase of progesterone and cortisol which leads to softening and stretching of the pelvic tissues9.

The case of pregnancy complicated with uterine prolapse presented here, is the only one which the obstetrics and gynecology clinic in Democritus University hospital was called to manage during the past 7 years. This woman suffered severe uterine prolapse of third degree, however an uncomplicated pregnancy and delivery was accomplished with a conservative treatment with pessary.

The management plan of uterine prolapse in pregnancy must be individualized and the obstetrician should consider the above mentioned possible complications. Bed rest in a slight Trendelenburg position should be advised in order to reduce edema and replacement of the uterus, good genital hygiene is imperative and local antiseptics could be used in case of an ulcerated and infected cervix and, following the accomplishment of reduction, continual use of a pessary is recommended, which should not be removed until the onset of labor9,11. Pessaries are available in a variety of shapes and sizes in order to suit different patients. There are two main types of pessaries; support pessaries (including ring, Gehrung, Hodge) and space occupying pessaries (cube, donut and Gellhorn)13. It is preferable to choose the largest pessary that the vaginal vault can accommodate. Reduction of the prolapsed uterus will protect the cervix from local trauma and prevent the possibility of incarceration. Furthermore, a pessary during the first stage of labor could prevent cervical dystocia and therefore the need for cervical Dührssen’s incisions9,11,14.

Labor induction with misoprostol or oxytocin is best to be avoided. Uterine fundal pressure to increase expulsive efforts in labor should not be performed as it could lead to calamitous consequences15,16. An elective cesarean section could be a safe mode of delivery, especially in cases with an edematous and elongated cervix12,17,18. For women who have completed their families Meydanli et al suggest the evasive approach of cesarian hysterectomy with the vaginal cuff is suspended to the periosteum overlying the sacral promontory after the procedure19.

A more “state of the art” approach was described by Matsumoto et al20 who performed laparoscopic uterine suspension in early gestation. Nevertheless, even minimally invasive therapy techniques in the gravid patient should have an approach where safety of the mother and fetus are both considered. Laparoscopy, once feared and contraindicated in pregnancy, has been gradually accepted and applied as more and more data supporting its safety and use have accumulated in the past decade. Without a doubt, laparoscopy and robotic assisted operations will radically alter the practice of obstetrics and gynecology in the 21st century21.

 

Conclusion

Uterine cervical prolapse concurrent with pregnancy is a rare event. The obstetrician should bear in mind the threat of preterm labor and delivery warrants close observation. However, literature review has a consensus that conservative treatment of these patients throughout pregnancy can result in an uneventful, normal, spontaneous delivery.

 

Conflict of interest:

All authors declare no conflict of interest.

 

References

  1. Tsikouras P, Dafopoulos A, Vrachnis N, et al. Uterine prolapse in pregnancy: risk factors, complications and management. J Matern Fetal Neonatal Med 2014;27:297 - 302. PubMed
  2. Swift S, Woodman P, O’Boyle A, et al. Organ Support Study (POSST): the distribution, clinical definition, and epidemiologic condition of pelvic organ support defects. Am J Obstet Gynecol 2005;192:795 - 806. PubMed
  3. Keettel WC. Prolapse of the uterus during pregnancy. Am J Obstet Gynecol 1941;42:121- 6.
  4. Van Dongen L. The anatomy of genital prolapse. S Afr Med J 1981;60:357 - 9. PubMed
  5. Jelovsek JE, Maher C, Barber MD. Pelvic organ prolapse. Lancet 2007;369:1027 - 38. PubMed
  6. Hendrix SL, Clark A, Nygaard I, Aragaki A, Barnabei V, McTiernan A. Pelvic organ prolapse in the Women’s Health Initiative: gravity and gravidity. Am J Obstet Gynecol 2002;186:1160 - 6. PubMed
  7. Thakar R, Stanton S. Management of genital prolapse. BMJ 2002;324:1258 - 62. PubMed
  8. DeLancey JO. The hidden epidemic of pelvic floor dysfunction: achievable goals for improved prevention and treatment. Am J Obstet Gynecol 2005;192:1488 - 95. PubMed
  9. Brown HL. Cervical prolapse complicating pregnancy. J Natl Med Assoc 1997;89:346 - 8. PubMed
  10. Behringer FR, Vigilante M. Uterine prolapse at term. Obstet Gynecol 1956;8:284 - 6. PubMed
  11. Piver MS, Spezia J. Uterine prolapse during pregnancy. Obstet Gynecol 1968;32:765 - 9. PubMed
  12. Daskalakis G, Lymberopoulos E, Anastasakis E, et al. Uterine prolapse complicating pregnancy. Arch Gynecol Obstet 2007;276:391- 2. PubMed
  13. Pott-Grinstein E, Newcomer JR. Gynecologists’ patterns of prescribing pessaries. J Reprod Med 2001;46:205 - 8. PubMed
  14. Klawans AH, Kanter AE. Prolapse of the uterus and pregnancy. Am J Obstet Gynecol 1949;57:939-46. PubMed
  15. Merhi ZO, Awonuga AO. The role of uterine fundal pressure in the second stage of labour: a reappraisal. Obstet Gynecol Surv 2005;60:599 - 603. PubMed
  16. Tukur J, Omale AO, Abdullahi H, Datti Z. Uterine prolapse following fundal pressure in the first stage of labour: a case report. Ann Afr Med 2007;6:194 - 6. PubMed
  17. Partsinevelos GA, Mesogitis S, Papantoniou N, Antsaklis A. Uterine prolapse in pregnancy: a rare condition an obstetrician should be familiar with. Fetal Diagn Ther 2008;24:296 - 8. PubMed
  18. Sze EH, Sherard GB 3rd, Dolezal JM. Pregnancy, labour, delivery and pelvic organ prolapse. Obstet Gynecol 2002;100:981 - 6. PubMed
  19. Meydanli MM, Ustün Y, Yalcin OT. Pelvic organ prolapse complicating third trimester pregnancy. A case report. Gynecol Obstet Invest 2006; 61:133 - 4. PubMed
  20. Matsumoto T, Nishi M, Yokota M, Ito M. Laparoscopic treatment of uterine prolapse during pregnancy. Obstet Gynecol 1999;93:849. PubMed
  21. Jackson H, Granger S, Price R, et al. Diagnosis and laparoscopic treatment of surgical diseases during pregnancy: an evidence-based review. Surg Endosc 2008;22:1917 - 27. PubMed

Fertility sparing options for women with ovarian neoplasms

Zygouris Dimitrios1, Panagopoulos Perikles1, Christodoulaki Chrysi1, Vrachnis Nikolaos2, Georgiou Athanasios1, Chrelias Charalampos1

1 3rd Department of Obstetrics and Gynecology, University of Athens, Medical School, Attiko hospital

2 2nd Department of Obstetrics and Gynecology, University of Athens Medical School, Aretaieio hospital

Correspondence: Zygouris Dimitrios, Papazoglou16, Ioannina, GR-45444, Greece. E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. 

 


 

Abstract

Ovarian cancer is the leading cause of death by gynecological cancer and it is estimated that up to 17% of cases occur in women less than 40 years. In these patients it is often vital to maintain their fertility. This can be achieved using either fertility sparing types of surgery under strict selection criteria, or in combination with methods of assisted reproduction. In any case this should be avoided in patients over 40 years, and patients should be fully aware of the potential oncology and reproductive outcome. It is also needed a comprehensive surgical staging and patient’s acceptance of a very close postoperative follow up. For patients with borderline tumor fertility sparing surgery is a safe option, with high percentages of achieved pregnancies and can be used either ovarian stimulation or ovarian tissue cryopreservation. In cases of invasive epithelial ovarian cancer fertility sparing clearly raises more concerns. The fertility surgery is recommended for patients with stage IA and low risk factors and under strict conditions for stages IB and IC, but beyond it is not considered safe choice. After surgery, pregnancy can be achieved by natural conception or assisted reproduction. In recent years there is growing debate on in vitro maturation of oocytes and growth to maintain fertility, making it a promising alternative. Furthermore, cryopreservation of ovarian tissue is discussed and has found application in several experimental studies, but without sufficient data. In conclusion, we should mention that many methods are at an early stage and clinicians should always personalize each patient’s treatment and provide full information about the chances of disease recurrence and the percentages of getting pregnant.

Key words: epithelial ovarian cancer; borderline ovarian tumor; fertility sparing; ovarian neoplasms

 

 

 

Every year about 200,000 new cases of ovarian cancer are diagnosed worldwide and 125,000 women die, even though the new chemotherapy regimens have greatly increased survival of patients with ovarian cancer1.

Approximately 10% to 15% of epithelial ovarian cancers have histological features and biological behavior between benign tumor and invasive cancer and are called low malignant potential (borderline tumors). The epithelial ovarian cancer including borderline tumors is 90% - 95% of cases and the remaining malignancies are of only 5% - 10%2. The cornerstone for the treatment of borderline tumors is the surgical removal. In cases of small size tumors the operation can be completed laparoscopically by experienced and well trained surgeons, or by classical laparotomic approach2. In women of childbearing age who have a strong desire to preserve their fertility is acceptable to perform a single resection with preservation of the uterus and the contralateral adnexa3, even in cases where the final diagnosis is invasive cancer stage I FIGO.

It is estimated that 10% of epithelial cancers develop in young women under the age of 402. In these patients is often vital to maintain their fertility. This can be achieved using either fertility sparing surgery with strict patient selection criteria or in combination with methods of reproductive medicine.

Since the appearance of a tumor in the ovary, surgical removal and staging is neccessary. The 1/3 of patients who appear to have disease in the ovary will be upstaged and will require postoperative chemotherapy. In patients with stage IA, IB grade 1 or 2, no further treatment is needed4. In this case, surgery can be performed in order to preserve fertility after selection of patients with strict criteria. Although the stage will increase in some patients, patients with stage I disease have excellent long-term survival after unilateral adnexectomy. Although in some cases chemotherapy is required, patients maintain their reproductive ability5.

 

Material and methods

For this literature review articles from the following electronic databases: pubmed, google scholar, Embase and Cochrane data base, have been used. The study also includes abstracts from international congresses and textbooks of Obstetrics - Gynecology, Gynecologic Oncology and Reproductive Medicine. In order to find the specific material we used the following keywords: epithelial ovarian cancer, Borderline ovarian tumors, fertility preservation, fertility sparing surgery and ovarian tissue cryopreservation.

The purpose of this literature review is the overall presentation of the available options to preserve fertility in cases of ovarian cancer. We introduce the already well-established fertility preservation techniques for some epithelial ovarian tumors, and new data from cases in recent years. Some are widely accepted and safe with adequate bibliographic data, while in other cases there are many controversies and doubts as a result of the small number of cases. We also report modern experimental techniques that are applied in cases of early stage ovarian cancer.

 

Preserving fertility in borderline tumors

Ovarian tissue cryopreservation is an excellent indication in borderline ovarian tumors, as this is a malignancy with excellent prognosis (5-year survival of 99% for stage I) occurring in young women6. Until now, conservative surgery is the gold standard in treatment of early stages of borderline tumors without peritoneal implantations. Moreover, surgery is an adequate treatment and it is rarely required as adjuvant chemotherapy. In stage I of the disease the recurrence rate is 5-10% and 30-45% in patients that have done adnexectomy or cystectomy respectively7.

Conservative surgery for borderline tumors includes cystectomy or adnexectomy, peritoneal washings cytology, peritoneum biopsies, and where appropriate omentectomy and appendectomy8,9. Fertility sparing surgery was originally applied to early stages of the disease and did not significantly affect the survival rates10-12. There were only higher rates of disease recurrence, suggesting the need for closer postoperative follow up of these patients. Fortin et al13 reported ovarian stimulation in 30 patients with borderline tumor, after fertility sparing surgery, with a median follow up of 23 months. They concluded that it is safe to use fertility drugs in these cases.

When a relapse occurs in the residual ovary the best way to preserve fertility is cystectomy. However, in many cases this conservative surgery is not technically feasible, because recurrence is bulky and the position of relapse does not allow conservative surgery. Since the cystectomy is feasible (residual ovary size in situ good for fertility) this is the perfect choice for maintaining fertility7, 14. Many authors have reported spontaneous conception and similar approach exists for patients with bilateral tumors at initial treatment.

There is growing interest in exploring ways of improving the fertility of patients in which preoperative indications show that a fertility sparing surgery is not feasible. If the patient has a partner he can go through an emergency IVF procedure. After completion of the procedure a surgery with purpose to remove the entire ovary and preserve the uterus follows. Such cases have been described with successful results in the literature13,15. Nevertheless, the safety of such an approach is very strongly doubted. Moreover, such a treatment can not be recommended in patients without a partner.

In such cases, another option is cryopreservation of ovarian tissue. But so far there are not enough publications with ovarian tissue cryopreservation in patients with Borderline tumors. One explanation for this is the reluctance of several research groups to date to suggest such an option for treating an ovarian tumor. The tumor is located in the organ which will be maintained raising many questions regarding safety and possible recurrence of the disease with re-implantation of cells in the future re-implantation of ovarian tissue sections. The risk of developing disease in cryopreserved tissue is extremely low in macroscopically normal ovarian tissue. The presence of microscopic disease in the contralateral ovary is low and Morice et al16 report that their initial experience in 14 patients showed no microscopic disease after tumor malignancy in the contralateral ovary. No patients experienced tumor cells in the part examined. However, the probability of cancer cells is increased in cases of serous papillary Borderline tumor and in advanced stage disease.

Fain-Kahn et al17 reported that in borderline tumors cryopreservation of ovarian tissue is feasible in 53%. The pregnancy rate after fertility sparing surgery ranged from 32% to 100%18,19. Table 1 shows the pregnancy rates reported in the literature after conservative treatment of borderline ovarian tumors. The conception was either automatic or subsequent IVF.

Other researchers have developed other techniques to avoid the risk of transmitting cancer cells from cryopreserved ovarian tissue. Conducting in vitro maturation (IVM) and follicular isolation is one option. IVM has been successful in one 43 years old patient with a borderline tumor20, but with low numbers of oocytes.

Where it is feasible to carry out cystectomy, there is no need for cryopreservation, as conservative surgery is considered the best option for preserving fertility. Furthermore, removal of ovarian tissue may result in infertility. Another reason for making cryopreservation is to find malignant recurrence in patients with a history of mucous borderline tumor. In these few common cases cryopreservation of ovarian tissue is recommended. We should also mention that technical reasons during the surgery may not allow adequate tissue retrieval for cryopreservation, especially when the ovary is occupied entirely by tumor.

The next step in maintaining fertility in Borderline tumors is to determine the minimum volume of residual ovarian tissue for freezing that is required to achieve the sufficient number of follicles thawing. In contrast there is a limitation of the potential existence of infiltration when taking the most of the ovaries6.


Fertility preservation in epithelial ovarian cancer

The increase in early gynecological control using ultrasound resulted in increased diagnosis of ovarian cancer at an early stage. Also, most women give birth to their first child in an older age, so the need for preserving fertility after diagnosis of early - stage ovarian cancer is growing. 3 - 17% of all epithelial ovarian cancers and 25% of stage I are in women under 40 years old21,22.

The surgery to maintain fertility is more aggressive than a simple unilateral adnexectomy. There is always risk of postoperative pelvic adhesions with potential to cause infertility. However, there are reports that there is no difference in the pregnancy rate23.

For patients with disease beyond stage IC fertility preservation is not considered as a safe option and should not be attempted. Park et al24 report 3 cases of patients with disease stage II and III which died from the disease 10 and 16 months respectively after the initial treatment.

Adjuvant chemotherapy in patients with stage I disease is necessary in unusual cell types with poor differentiation and stage IC25,26. The adjuvant chemotherapy is therefore an important factor of treatment to preserve fertility but should be added only in patients with high risk factors.

Morice et al27 reported 33 patients with stage I disease who underwent unilateral adnexectomy. There were 11 recurrences of which 7/30 (23%) were stage IA and 3/3 (100%) IC. For this reason they do not recommend making adnexectomy in stage bigger than IA. However, the number of patients with IC disease or IA/G3 was too small to draw reliable conclusions. Worth mentioning is the fact that in 3 patients the relapses were in remote areas without any disease in the remaining ovary.

Instead, Schilder et al5 reported 42 cases of stage IA and 10 of stage IC which underwent fertility sparing surgery in 8 different centers. There was one recurrence in 10 patients (10%) with stage IC. Moreover, Zanetta et al28 in a series of 22 stage IC cases found one relapse (1/22, 4.5%) in the pelvic area and recommend fertility sparing surgery even for patients with stage IC. In another study, Kajiyama et al23 did not report any difference in overall survival and disease-free survival among patients with stage IA and IC.

The fertility sparing surgery in patients with stage IB disease is extremely rare. If it is desired to maintain the contralateral ovary at this stage is necessary to remove the tumor from the ovarian tissue with partial resection. However, it may remain in the tumor cells in the residual ovary, despite the intraoperative macroscopic and microscopic examination. Kajiyama et al23 reported a case of recurrence and death from peritoneal carcinomatosis after a long time. Unlike, Park et al24 reported two cases of patients without any evidence of recurrence, while Colombo et al29 and Zanetta et al28 reported each one case without any evidence of recurrence. Since the number of cases is too small it is very difficult to draw conclusions about safety at this stage of the disease. The fertility sparing surgery can be considered safe when there is a good portion of ovarian tissue remaining24. Though, we always have to keep in mind the possible increased risk of disease recurrence.

The selection of patients for fertility preservation is based largely on the stage of disease. For this reason a complete surgical staging is needed. Up to 30% of patients with presumed early stage disease were up staged after thorough staging surgery, due to microscopic metastases in the peritoneal washings, lymph nodes, omentum or the diaphragm30. If the patient is not completely staged, this is a negative prognostic factor31, while complete staging is necessary to avoid possible adjuvant chemotherapy.

The standard procedure involves pelvic and para-aortic lymphadenectomy, omentectomy, peritoneal washings cytology, multiple peritoneal biopsies and possibly appendectomy. There are several controversies about the necessity of lymphadenectomy and appendectomy. The incidence of pelvic and para - aortic lymph node metastases is 8 - 30% in an apparent early stage30, 32. Cass et al33 found that 21% of patients with pelvic or para-aortic lymph node metastases were found on the opposite side from that which was the original disease. These data demonstrate the necessity of systematic lymphadenectomy in the staging surgery34,35. The appendectomy in the early stage of disease and non-mucous tumors offers no proven benefit in many centers is still optional24,36.

Another controversial point is how to evaluate the contralateral ovary. Munnel et al6 calculated that the probability of a hidden disease in macroscopically normal ovary is 12%. Moreover, Benjamin et al37 reported a 2.5% presence of microscopic disease in the contralateral ovary. Schlaerth et al38 evaluated the contralateral ovary macroscopically with wedge biopsy and cystectomy and found no infiltration of the contralateral ovary in 20 cases. Also Colombo et al29 and Zanetta et al28 by performing a biopsy of the contralateral ovary did not find any disease.

An important issue that has been reported is the possibility of infertility and ovarian failure after a wedge biopsy16. Overall, however, careful inspection and biopsy of the contralateral ovary is considered adequate and safe procedure.

The evaluation of the endometrium is another important parameter to diagnose a hidden disease. There is always the possibility of sychronous endometrial cancer or extension of ovarian cancer in the endometrium, especially in cases of endometrioid ovarian cancer. For this reason, it is recommended endometrial biopsy during the surgical staging, especially in patients with endometrioid ovarian cancer. Park et al24 reported that in 8 cases of endometrioid tumor, endometrial cancer cells were not found in any case, while Schlaerth et al38 in 14 cases found no development of carcinoma at the time of surgery, but one patient developed endometrial cancer 15 months after surgery. Zaino et al39 found coexistence of endometrial cancer in endometrioid carcinomas at a rate of 10%. Therefore endometrial biopsy is recommended as part of the fertility sparing surgery.

The histologic grade (differentiation) is another prognostic factor in an early stage disease31. Fertility preservation is considered safe only in cases of grade I and II and not grade III, even if it is stage IA that will receive chemotherapy. The histological type is also an important prognostic factor6. Park et al24 reported 4 patients with clear cell ovarian cancer, of which 2 (stage IA) relapsed and died from the disease. For this reason fertility sparing surgery is not recommended in such aggressive histological types6.

Another important controversy is whether after completion of the childbearing (or after the age of 40 years) a total hysterectomy and adnexectomy must be performed. The decision should be individualized for each patient, taking into account all prognostic factors; considering that the possibility of late recurrence is not negligible. Morice et al 27 mentioned the latest relapse after more than 10 years. It is necessary to follow up closely these patients every 3 months for the first 2 years and then every 6 months. The check should include ultrasonography and tumor markers. Several researchers recommend delaying radical surgery to menopause as a logical decision24, 40.

In addition fertility preservation by preserving the uterus and the adnexa has non-reproductive benefits. A recent meta - analysis showed risk reduction for cardiovascular diseases41.

Table 2 shows the articles with achieved pregnancies. Satoh et al42 reported the biggest number of patients so far (211), with 76 achieved pregnancies. Park et al24 mentioned that all 62 patients had menstruation after surgery while most patients who achieved pregnancy they did it without any birth defect, despite the increased proportion of patients receiving chemotherapy. Also Schlaerth et al38 reported 6 patients that achieved pregnancies .

The ovarian tissue cryopreservation as an alternative to preserve fertility is still an experimental procedure. There are no data yet for firm conclusions, only a few report describing the application of the method in epithelial ovarian cancer43.

 

tables 12

 

Conclusion

Preserving fertility in patients with ovarian tumor should be performed with strict criteria selection of patients, based on the histological type of disease and prognostic factors. In any case this should be avoided in patients over 40 years and patients should be fully aware of the potential oncological and reproductive outcome. Also it is necessary a comprehensive surgical staging and the patient’s acceptance of a very close postoperative follow up.

For patients with borderline tumor fertility sparing surgery is a safe option. It is quite common to achieve a pregnancy after natural conception, and more rarely may require ovarian stimulation and IVF. Another alternative with very encouraging results is the cryopreservation of ovarian tissue and use it thereafter.

For invasive epithelial ovarian cancer fertility preservation clearly raises more concerns. Fertility preservation surgery is recommended for patients with stage IA and low risk factors and under strict conditions for stages IB and IC, but not beyond what is considered a safe choice. After surgery, pregnancy can be achieved by natural conception or assisted reproduction. The use of drugs for stimulation is also highly questionable. In recent years there is growing debate on in vitro maturation of oocytes and development to maintain fertility, making it a promising alternative. Furthermore, cryopreservation of ovarian tissue is discussed and has found application in several experimental studies, but without sufficient data. Main concern is the re-implantation of cancer cells and the direction of researchers is to find a safe method of screening for potential tumor cells. There are also prospects for the use of cryopreserved ovarian tissue to obtain oocytes for further use in the reproductive process.

We must always keep in mind that all these methods are at an early stage and we should always personalize the treatment of each patient. In addition the patient should be fully informed of the chances of disease recurrence and the pregnancy rates.

 

Conflict of interest

All authors declare no conflict of interest.

 

 

References

  1. Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380:2095 - 128. PubMed
  2. Jayson GC, Kohn EC, Kitchener HC, Ledermann JA. Ovarian cancer. Lancet 2014;384:1376 - 88. PubMed
  3. Zanetta G, Rota S, Lissoni A, Meni A, Brancatelli G, Buda A. Ultrasound, physical examination, and CA 125 measurement for the detection of recurrence after conservative surgery for early borderline ovarian tumors. Gynecol Oncol 2001;81:63 - 6. PubMed
  4. Shroff R, Brooks RA, Zighelboim I, et al. The utility of peritoneal biopsy and omentectomy in the upstaging of apparent early ovarian cancer. Int J Gynecol Cancer 2011;21:1208 - 12. PubMed
  5. Schilder JM, Thompson AM, DePriest PD, et al. Outcome of reproductive age women with stage IA or IC invasive epithelial ovarian cancer treated with fertility-sparing therapy. Gynecol Oncol 2002;87:1 - 7. PubMed
  6. Morice P, Denschlag D, Rodolakis A, et al; Fertility Task Force of the European Society of Gynecologic Oncology. Recommendations of the Fertility Task Force of the European Society of Gynecologic Oncology about the conservative management of ovarian malignant tumors. Int J Gynecol Cancer 2011;21:951- 63. PubMed
  7. Morice P. Borderline tumours of the ovary and fertility. Eur J Cancer 2006;42:149 - 58. PubMed
  8. Nam JH. Borderline ovarian tumors and fertility. Curr Opin Obstet Gynecol 2010;22:227 - 34. PubMed
  9. Cadron I, Leunen K, Van Gorp T, Amant F, Neven P, Vergote I. Management of borderline ovarian neoplasms. J Clin Oncol 2007;25:2928 - 37. PubMed
  10. Fauvet R, Boccara J, Dufournet C, Poncelet C, Daraï E. Laparoscopic management of borderline ovarian tumors: results of a French multicenter study. Ann Oncol 2005;16:403 -10. PubMed
  11. De Iaco P, Ferrero A, Rosati F, et al. Behaviour of ovarian tumors of low malignant potential treated with conservative surgery. Eur J Surg Oncol 2009;35:643 - 8. PubMed
  12. Zanetta G, Rota S, Chiari S, Bonazzi C, Bratina G, Mangioni C. Behavior of borderline tumors with particular interest to persistence, recurrence, and progression to invasive carcinoma: a prospective study. J Clin Oncol 2001;19:2658 - 64. PubMed
  13. Fortin A, Morice P, Thoury A, Camatte S, Dhainaut C, Madelenat P. Impact of infertility drugs after treatment of borderline ovarian tumors: results of a retrospective multicenter study. Fertil Steril 2007;87:591- 6. PubMed
  14. Fauvet R, Poncelet C, Boccara J, Descamps P, Fondrinier E, Daraï E. Fertility after conservative treatment for borderline ovarian tumors: a French multicenter study. Fertil Steril 2005;83:284 - 90. PubMed
  15. Gallot D, Pouly JL, Janny L, et al. Successful transfer of frozen-thawed embryos obtained immediately before radical surgery for stage IIIa serous borderline ovarian tumour: case report. Hum Reprod 2000;15:2347 - 50. PubMed
  16. Morice P, Camatte S, El Hassan J, Pautier P, Duvillard P, Castaigne D. Clinical outcomes and fertility after conservative treatment of ovarian borderline tumors. Fertil Steril 2001;75:92 - 6. PubMed
  17. Fain-Kahn V, Poirot C, Uzan C, et al. Feasibility of ovarian cryopreservation in borderline ovarian tumours. Hum Reprod 2009;24:850 - 5. PubMed
  18. Demeter A, Csapó Z, Szánthó A, Bálega J, Sipos N, Papp Z. A retrospective study of 27 ovarian tumors of low malignant potential. Eur J Gynaecol Oncol 2002;23:415 - 8. PubMed
  19. Chan JK, Lin YG, Loizzi V, Ghobriel M, DiSaia PJ, Berman ML. Borderline ovarian tumors in reproductive-age women. Fertility-sparing surgery and outcome. J Reprod Med 2003;48:756 - 60. PubMed
  20. Huang JY, Buckett WM, Gilbert L, Tan SL, Chian RC. Retrieval of immature oocytes followed by in vitro maturation and vitrification: a case report on a new strategy of fertility preservation in women with borderline ovarian malignancy. Gynecol Oncol 2007;105:542 - 4. PubMed
  21. Duska LR, Chang YC, Flynn CE, et al. Epithelial ovarian carcinoma in the reproductive age group. Cancer 1999;85:2623 - 9. PubMed
  22. Rodriguez M, Nguyen HN, Averette HE, et al. National survey of ovarian carcinoma XII. Epithelial ovarian malignancies in women less than or equal to 25 years of age. Cancer 1994;73:1245 - 50. PubMed
  23. Kajiyama H, Shibata K, Suzuki S, et al. Fertility-sparing surgery in young women with invasive epithelial ovarian cancer. Eur J Surg Oncol 2010;36:404 - 8. PubMed
  24. Park JY, Kim DY, Suh DS, et al. Outcomes of fertility-sparing surgery for invasive epithelial ovarian cancer: oncologic safety and reproductive outcomes. Gynecol Oncol 2008;110:345 - 53. PubMed
  25. Le T, Krepart GV, Lotocki RJ, Heywood MS. Clinically apparent early stage invasive epithelial ovarian carcinoma: should all be treated similarly? Gynecol Oncol 1999;74:252 - 4. PubMed
  26. Young RC, Walton LA, Ellenberg SS, et al. Adjuvant therapy in stage I and stage II epithelial ovarian cancer. Results of two prospective randomized trials. N Engl J Med 1990;322:1021 - 7. PubMed
  27. Morice P, Leblanc E, Rey A, et al. Conservative treatment in epithelial ovarian cancer: results of a multicentre study of the GCCLCC (Groupe des Chirurgiens de Centre de Lutte Contre le Cancer) and SFOG (Société Francaise d’Oncologie Gynécologique). Hum Reprod 2005;20:1379 - 85. PubMed
  28. Zanetta G, Chiari S, Rota S, et al. Conservative surgery for stage I ovarian carcinoma in women of childbearing age. Br J Obstet Gynaecol 1997;104:1030 - 5. PubMed
  29. Colombo N, Chiari S, Maggioni A, Bocciolone L, Torri V, Mangioni C. Controversial issues in the management of early epithelial ovarian cancer: conservative surgery and role of adjuvant therapy. Gynecol Oncol 1994;55:S47 - 51. PubMed
  30. Park JY, Kim DY, Suh DS, et al. Comparison of laparoscopy and laparotomy in surgical staging of early-stage ovarian and fallopian tubal cancer. Ann Surg Oncol 2008;15:2012 - 9. PubMed
  31. Zanetta G, Rota S, Chiari S, et al. The accuracy of staging: an important prognostic determinator in stage I ovarian carcinoma. A multivariate analysis. Ann Oncol 1998;9:1097 - 101. PubMed
  32. Tsumura N, Sakuragi N, Hareyama H, et al. Distribution pattern and risk factors of pelvic and para-aortic lymph node metastasis in epithelial ovarian carcinoma. Int J Cancer 1998;79:526 - 30. PubMed
  33. Cass I, Li AJ, Runowicz CD, Fields AL, et al. Pattern of lymph node metastases in clinically unilateral stage I invasive epithelial ovarian carcinomas. Gynecol Oncol 2001;80:56 - 61. PubMed
  34. Benedetti-Panici P, Greggi S, Maneschi F, et al. Anatomical and pathological study of retroperitoneal nodes in epithelial ovarian cancer. Gynecol Oncol 1993;51:150 - 4. PubMed
  35. Petru E, Lahousen M, Tamussino K, et al. Lymphadenectomy in stage I ovarian cancer. Am J Obstet Gynecol. 1994;170:656 - 62. PubMed
  36. Ramirez PT, Slomovitz BM, McQuinn L, Levenback C, Coleman RL. Role of appendectomy at the time of primary surgery in patients with early-stage ovarian cancer. Gynecol Oncol 2006;103:888 - 90. PubMed
  37. Benjamin I, Rubin SC. Management of early-stage epithelial ovarian cancer. Obstet Gynecol Clin North Am 1994;21:107 - 19. PubMed
  38. Schlaerth AC, Chi DS, Poynor EA, Barakat RR, Brown CL. Long-term survival after fertility-sparing surgery for epithelial ovarian cancer. Int J Gynecol Cancer 2009;19:1199 - 204. PubMed
  39. Zaino R, Whitney C, Brady MF, DeGeest K, Burger RA, Buller RE. Simultaneously detected endometrial and ovarian carcinomas - a prospective clinicopathologic study of 74 cases: a gynecologic oncology group study. Gynecol Oncol 2001;83:355 - 62. PubMed
  40. Wright JD, Shah M, Mathew L, et al. Fertility preservation in young women with epithelial ovarian cancer. Cancer 2009;115:4118 - 26. PubMed
  41. Atsma F, Bartelink ML, Grobbee DE, van der Schouw YT. Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: a meta-analysis. Menopause 2006;13:265 - 79. PubMed
  42. Satoh T, Hatae M, Watanabe Y, et al. Outcomes of fertility-sparing surgery for stage I epithelial ovarian cancer: a proposal for patient selection. J Clin Oncol 2010;28:1727 - 32. PubMed
  43. Klock SC, Zhang JX, Kazer RR. Fertility preservation for female cancer patients: early clinical experience. Fertil Steril 2010;94:149 - 55. PubMed