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Discovery promises early diagnosis of endometriosis

Discovery promises early diagnosis of endometriosis

By I.Soussis, MD, MSc, FRCOG, Fertility Specialist

 

Scientists from the Feinstein Institute for Medical Research announced an experimental, rapid and non-invasive way to diagnose endometriosis, which may lead to earlier and more effective treatments for this disorder that affects approximately 176 million women globally.

The scientists found that a particular feature of cells found in menstrual blood suggests that a patient has endometriosis, according to findings published in Molecular Medicine.

The simple test uses menstrual blood and takes only a few days to report. This is a dramatic improvement over current diagnostic methods that rely on laparoscopy, which patients try to avoid, delaying diagnosis typically five to 10 years from the onset of symptoms.

Endometriosis is a chronic condition in which the endometrium grows outside the uterus, typically in the abdominal cavity or on internal organs. Patients often experience significant pain and discomfort during their period or intercourse.  Endometriosis may also lead to infertility or hysterectomy.

Researchers at the Feinstein Institute established the Research Out-Smarts Endometriosis (ROSE) program to study the genetic basis of endometriosis and what is occurring at the cellular level in this disease. As part of ROSE, healthy women and others with endometriosis, provide peripheral and menstrual blood samples which are stored in a biobank so that they can be analysed in current and future research studies.

The recently-published study focused on the role of stromal fibroblasts, a type of stem cell found in menstrual blood, and the immune system. Professors Christine N.Metz, PhD and Peter K.Gregersen, MD, along with Laura A. Warren, an MD-PhD student at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell have led this research effort.

“The cause of endometriosis is not known. One theory is retrograde menstruation, which is where menstrual blood containing uterine tissue is transported into the abdominal cavity instead of out of the body. Almost all women experience retrograde menstruation, but we’re unsure why in some women this endometrial tissue latches on to the abdominal wall and internal organs and grows causing endometriosis,” said Dr. Metz. “In this study, we found that the stem cells in the menstrual blood of women with endometriosis are very different from those of healthy women and we are learning from these differences to develop a novel non-invasive diagnostic test.”

Metz and her colleagues observed that the menstrual blood of endometriosis patients contained a significantly smaller number of uterine natural killer (uNK) cells compared with healthy participants. In addition to this decrease, they observed that endometriosis patients’ stem cells showed impaired decidualization, a process that prepares the uterus for embryo implantation.

“Instead of having to undergo surgery to accurately diagnose endometriosis, these findings will enable us to develop a rapid test for endometriosis based on menstrual blood, which can be easily collected. This will allow medical professionals to know if someone is at risk of developing endometriosis and start treatment sooner, and it will help them monitor patients’ responses to treatment,” said Dr. Gregersen. “Endometriosis is a chronic, complex condition and improved understanding of this disease through studying menstrual blood is likely to drive personalization of new therapies.”

 

You can read the data published in Molecular Medicine, here:

https://molmed.biomedcentral.com/articles/10.1186/s10020-018-0009-6.

Source: https://www.feinsteininstitute.org/2018/03/feinstein-institute-discovery-promises-improved-diagnosis-understanding-endometriosis/

Image credit: http://healthizmo.com/endometriosis-what-you-need-to-know

Women with endometriosis and diffuse adenomyosis at higher risk for smaller babies, study suggests

Women with endometriosis and diffuse adenomyosis at higher risk for smaller babies, study suggests

By I.Soussis, MD, MSc,FRCOG

Fertility Specialist

Researchers have found that pregnant women with both endometriosis and diffuse adenomyosis have a nearly four times greater risk of carrying a baby that is small for its gestational age.

The study from Italy, was published in the journal Ultrasound in Obstetrics and Gynecology.

In the last decade, many studies have reported an association between endometriosis and major pregnancy-related complications, including spontaneous late miscarriage, preterm labor, fetuses small for gestational age (SGA), hypertension, pre-eclampsia, and other issues. But other studies have not reached similar conclusions.

Endometriosis is the disease that the endometrium, the tissue lining the uterus is located outside the uterus. Often is accompanied by adenomyosis, which refers to a condition where the tissue lining the uterus grows into the muscular wall of the uterus.

The reported prevalence of adenomyosis in patients with endometriosis ranges from 20% to 50%. Previous studies have shown that adenomyosis can lead to an increased risk of adverse events in pregnancy, but few studies have paid close attention to the correlation between adenomyosis and pregnancy outcomes in patients with concurrent endometriosis.

Researchers set out to determine whether the maternal and fetal outcomes were different in women with endometriosis alone compared to endometriosis with either diffuse or focal adenomyosis.

Focal adenomyosis occurs in one particular site of the uterus, while diffuse adenomyosis is when the condition is spread throughout the uterus.

Researchers conducted a retrospective analysis of 206 pregnant women with endometriosis, of which 71.8% had endometriosis alone, 18.4% had endometriosis with focal adenomyosis (EFA) and 9.7% had endometriosis with diffuse adenomyosis (EDA).

Conventional risk factors associated with placental insufficiency such as BMI, PAPP-A levels, and mean uterine artery pulsatility index (UtA PI) in the first and the second trimester were found to be significantly associated with EDA, compared to patients with endometriosis alone. There were no statistically significant differences found in EFA patients.

 Interestingly, an analysis showed that EDA was the only independent risk factor for babies who were small for gestational age (SGA), with an overall higher risk of 3.74 in women with EDA compared to those with endometriosis alone.

SGA is a term used to describe a fetus that is smaller than average for the number of weeks of pregnancy.

One explanation for this result is that women with adenomyosis have imbalanced blood flow, with higher blood flow to the uterine adenomyosis area and lower blood flow to the placenta, which could lead to the reduced growth of the fetus.

“The current study shows that diffuse adenomyosis in pregnant women with endometriosis is strongly associated with SGA infants,” the study’s authors concluded.

They added that women with EDA should be treated as high-risk patients for placental dysfunction and should be more closely monitored.

Source: https://endometriosisnews.com/2018/01/03/women-endometriosis-diffuse-adenomyosis-higher-risk-smaller-babies/

Image credit:https://www.healthline.com/health/pregnancy/getting-pregnant-with-endometriosis

Breast feeding linked to lower risk of endometriosis

Breast feeding linked to lower risk of endometriosis

 

BY I. SOUSSIS MD

FERTILITY SPECIALIST

A new study, which followed more than 72 thousand women for more than 20 years, has found that breast feeding is linked to a lower risk of being diagnosed with endometriosis.

Researchers found that among the 72,394 women who had one or more pregnancies (that lasted at least 6 months) there were 3,296 laparoscopically confirmed cases of endometriosis. Compared with women who nursed for less than a month per pregnancy, those who nursed for a year or more had a 32% reduced risk of endometriosis. For each additional three months of breast feeding, the risk was reduced by 8%.

The association between the risk reduction and breast feeding may be mediated at least in part by amenorrhea, according to the researchers who analyzed data from Nurses’ Health Study II (NHS II).

The study, led by Brigham and Women’s Hospital (BWH) in Boston, MA, and published in the British Medical Journal. It is the largest study to date on the link between breast feeding and the risk of endometriosis.

A 40% reduced risk of endometriosis was seen in women who breastfed for ≥ 36 months during their reproductive lives versus women who never breastfed.

Incidence of endometriosis was 453 per 100,000 person-years in the women who breastfed for less than a month versus 184 per 100,000 person-years for those who reported a lifetime total ≥ 36 months. Every additional 3 months of total breastfeeding per pregnancy was associated with an 8% lower risk of endometriosis. A 14% lower risk of endometriosis was seen for every additional 3 months of exclusive breastfeeding.

The protective association with breast feeding was strongest among women who had given birth within the last 5 years. Postpartum amenorrhea partially influenced the association with breastfeeding (34% total breast feeding and endometriosis and 57% for exclusive breast feeding and endometriosis).

Endometriosis is a chronic, incurable gynecologic disorder that affects girls and women. The disorder arises when tissue that is similar to the lining of the uterus (endometrium) is found attached to other areas in the body, generally in the pelvic cavity. As a result, most women with endometriosis experience “chronic pelvic pain, painful periods, and pain during intercourse.

 

A new non-invasive diagnostic test for endometriosis

A new non-invasive diagnostic test for endometriosis

A revolutionary new diagnostic test for endometriosis will shortly be released by an American company. The test developed by the San Francisco based company uses the patient’s saliva to look for particular biomarkers found to be elevated in endometriosis patients.

Endometriosis is a chronic condition where the tissue that lines the womb (called endometrium) grows outside of the womb. This ectopic tissue then bleeds at the same time as a normal period and causes pain. 

Endometriosis is extremely difficult to diagnose due to overlapping symptoms with other gynaecological conditions and usually, there is a long delay from the first appearance of symptoms to a definitive diagnosis.

Currently, the only way to diagnose endometriosis is through laparoscopy, so the availability of such a simple non-invasive test would be welcomed by patients and clinicians alike. 

American company Dotlab announced it will mail a saliva test kit to the patient’s home. The patient then will mail the saliva sample back to them and later get their results through a secure online dashboard.

There is no data available as yet about the reliability of the saliva-based test but the company claims it has been tested on thousands of patients to date. 

The development of the test seems to have stemmed from much research the company has carried out into the levels of molecules called microRNAs present in the blood. 

The levels of these molecules could be used to accurately predict a surgically achieved diagnosis of endometriosis in those suspected of having the condition. 

Dr. Hugh Taylor, Chair of Obstetrics, Gynecology, and Reproductive Sciences at the Yale School of Medicine, Chief Medical Officer and co-founder of Dotlab said: “Diagnostic biomarkers for endometriosis have the potential to dramatically reduce the time from the onset of symptoms to effective diagnosis and management.” Dr. Taylor also said that once diagnosed, the test could be used for ongoing monitoring of the disease, “These biomarkers could be used to not only identify patients requiring medical or surgical treatment but also to monitor treatment response and recurrence of the disease.”

At present, there is only an early access program allowing some clinicians to get their hands on the kit. The company has not announced a general release date or if the test will be available throughout the world.

 

Obstetric complications in women with endometriosis

Image courtesy of imagerymajestic at FreeDigitalPhotos.net

Image courtesy of imagerymajestic at FreeDigitalPhotos.net

Obstetric complications in women with endometriosis

By I.Soussis MD

Women with endometriosis present an increased chance of complications during pregnancy, compared to those without.

A large Swedish study comprised of 8.922 women with endometriosis, who gave birth to 13.090 children (single pregnancies) was compared to 1.4 million births of children obtained from the National Birth Records Office.

When women without endometriosis were compared to women with endometriosis, it was found that the latter were at increased risk regarding:

Premature labour.  The risk is increased 1.24 times in women that got pregnant with IVF and 1.37 times in those with spontaneous conception.

Preeclampsia.  Increased risk by 1.13 times.

Placental abruption- haemorrhage.   Increased risk 1.76 times

Caesarian section.  Increased risk by 1.47 times

This study found no relation between endometriosis and underweight babies or intrauterine death.

Professor P.Barri from the University of Barcelona, presented his results at the 6th National Conference IVI in Alicante 2015.

The complications of pregnancy of 118 women, who had gotten pregnant with IVF due to endometriosis, were compared to 118 women who got pregnant with IVF due to male factors and 10.633 spontaneous pregnancies.

The percentage of gestational diabetes mellitus, fetal macrosomia and Caesarian section rates, showed no significant differences in the three groups.

It remains to be seen, if the increased risks that were mentioned are due to endometriosis itself, infertility or IVF.

Sebutal et al. carried out a systematic retrospective review of  studies, regarding complications of pregnancy in women with deep infiltrating endometriosis. They found 12 articles describing the spread of deep infiltrating endometriosis during pregnancy and one article describing six cases of bowel obstruction during IVF.

Despite the fact that traditionally, pregnancy was regarded as a treatment for endometriosis, this is not the case in some women.

The mentioned complications are severe, but rare. Although the chance of their occurrence can not be ruled out.

Fertil Steril. 2014 Feb;101(2):442-6. doi: 10.1016/j.fertnstert.2013.11.001. Epub 2013 Dec 18. Bowel complications of deep endometriosis during pregnancy or in vitro fertilization. Setúbal A1, Sidiropoulou Z2, Torgal M3, Casal E3, Lourenço C4, Koninckx P5.

Hum Reprod. 2009 Sep;24(9):2341-7. doi: 10.1093/humrep/dep186. Epub 2009 May 12. Endometriosis, assisted reproduction technology, and risk of adverse pregnancy outcome. Stephansson O1, Kieler H, Granath F, Falconer H.

BARRI.P, 6th International Congress IVI Alicante Spain 23-25 April,2015 Reproductive Medicine and beyond

How successful is egg donation in women with endometriosis?

By I.Soussis MD

Egg donation is a fantastic tool in our hands, that allows us to explore how endometriosis affects the results of IVF.

Its action is through the endometrium or through the quality of the oocytes and subsequently through the quality of the produced embryos?

In trying to answer the question two different approaches have been taken:

1. The eggs of the same donor were shared by two recipients. One recipient is healthy and the other suffers from endometriosis. Data was prospectively collected and the pregnancy rates between the two groups compared.

2. Retrospective studies with oocyte donation cycles, in which a recipient became pregnant and the other not. The data was analyzed according  to the cause of infertility. We also examined the origin of the eggs and compared the pregnancy rates between recipients, receiving ova from donors with endometriosis or without endometriosis.

Diaz et al 2000, from the Valencia Infertility Institute IVI IVF studied 58 recipients. Of these 25 were suffering from severe endometriosis stage III and IV. The remaining 33 recipient did not suffer from endometriosis. Both groups of women followed the same preparation of the endometrium, prior to embryo transfer. The number of fertilized eggs, of transferred embryos, the pregnancy rates and abortion rates were similar in both groups. So severe endometriosis does not affect pregnancy rates when the eggs come from healthy donors.

Similar results were reported from 444 egg donation cycles in 222 recipients from Bodri et al 2007.

Simon et al. 1994 again from I.V.I IVF retrospectively examined 178 embryo transfers into 141 recipients. Significantly lower pregnancy rates were found in women who received oocytes from donors with endometriosis.

To further investigate the influence of endometriosis on the endometrium or the egg, the same group of scientists in Spain, organized a prospective study Pelicer et al 1994.

Patients were divided into three groups. A: 44 donors without endometriosis who gave eggs to healthy recipients, B: 14 donors with endometriosis who gave eggs to healthy recipients, and C: 16 donors without endometriosis donated to recipients with endometriosis.

Significantly lower embryo implantation rates were observed in group B 6.8% versus 20.1% A and 20.8% C.

Significantly lower rates of pregnancy were observed in group B 28.6% vs. 61.4% A and 60% C.

Budak et al 2007 studied retrospectively> 10,000 oocyte donation cycles over a period of 10 years. They confirmed that pregnancy rates in recipients with endometriosis were identical to those women without endometriosis.

In agreement with the mentioned studies, analysis of the results of egg donation  in our IVF Unit in Athens, IVF & Genetics, showed that the recipients with endometriosis have excellent pregnancy rates of 60%.

Conclusions:

1. Pregnancy rates after oocyte donation in recipients with endometriosis are excellent, when the eggs originate from donor without endometriosis and they can reach 61.4%.

2. Pregnancy rates after oocyte donation are lower than expected, even in healthy recipients, when the eggs originate from donors with endometriosis.

3. Endometriosis affects the quality of the eggs.

 

 

 

How successful is intrauterine insemination in women with endometriosis?

By I. Soussis MD

How successful is intrauterine insemination in infertile women with endometriosis?

Tummon et al. 1997 enrolled 103 infertile couples with endometriosis stage I and II in a prospective randomized  study. Of those patients 53 underwent superovulation treatment with gonadotrophins and intrauterine insemination (127 cycles) and  the remaining 50 were the control group and were just observed for 184 cycles. The birth rate in the treatment group were 5-6 higher than the controls.

Cumulative pregnancy rate. Women with IUI and superovulation versus no treatment

Cumulative pregnancy rate.
Women with IUI and superovulation versus no treatment

In another study, initially randomized, Nulsen et al. 1993, compared superovulation with gonadotrophins and intrauterine insemination with insemination without superovulation.

The success rate was 5.7 times higher in the superovulation group.

Werbrouck et al. 2006, studied infertile women with endometriosis, who were treated with gonadotrophins and intrauterine insemination within six months from their laparoscopy. They reported pregnancy rates similar to those with unexplained infertility (20% vs 20,5%).

ESHRE Guidelines 2015:

1. Superovulation with gonadotrophins and intrauterine insemination in infertile women with endometriosis stage I and II increases the birth rate compared with conservative management (observation).

2. Superovulation with gonadotrophins and intrauterine insemination in infertile women with endometriosis stage I and II increases the birth rate compared with intrauterine insemination alone.

3. Superovulation with gonadotrophins and intrauterine insemination in infertile women with endometriosis, within six months of laparoscopy, is equally effective as in those with unexplained infertility.

Good Practice Point (opinion of the ESHRE specialists). IVF treatment is advised if there is tubal factor, sperm problems or other treatment have failed.

How endometriosis is poisoning the ovary?

By I.Soussis MD

The reputable journal Human Reproduction Update in  2014 published an excellent study by ΑΜ Sanchez et al., on how an endometrioma ( a chocolate cyst) affects the surrounding healthy ovarian tissue. They reviewed the scientific literature of the last 25 years on the subject. They excluded all the clinical articles and they focused on what is known on basic science.

The endometrioma contains toxic substances such as free iron, free oxygen radicals, proteolytic enzymes and chemicals of inflammation in a concentration of tens and even hundreds of times higher, than those in blood or in non endometriotic benign cysts.

The concentration of CA-125 in the endometriotic cyst is 100 times higher than in the blood. The reason why this happens is unknown. It is however known that the CA-125 is a strong indicator of inflammation.

Toxic factors affect the endometriotic cells with which they come into contact. They may alter their gene expression or they can even cause genetic mutations.

The wall of the chocolate cyst is thin and consists of connective tissue and the cortex of the ovary.

Oxygen free radicals (which are powerful cellular stress factors), proteolytic enzymes and other toxic substances diffuse through the cyst wall to the adjacent healthy ovarian tissue. The healthy ovary is reacting with the creation of scar tissue, in an attempt to limit the damage.

The smooth muscle fibers in the region undergo metaplasia and the small vessels of the ovary also sustain damages . As a consequence of the vascular lesions, the follicles are not fed properly, they do not mature and finally they regress. Their numbers decrease.

Indeed many histological studies have shown reduced follicular density  in the ovary, in areas neighboring with ovarian endometriomas.

Now we believe that the damage of the ovary is more due to the action of these toxic agents, rather than the stretching of the tissues, caused by the cyst.

Knowledge of the pathophysiology can lead to the introduction of new drug therapies, that neutralize the action of these toxic agents. We could thus protect the ovary from damages caused by endometriosis.

The distinguishing cellular and molecular features of the endometriotic ovarian cyst: from pathophysiology to the potential endometrioma-mediated damage to the ovary A.M. Sanchez1, P. Viganò2,*, E. Somigliana3, P. Panina-Bordignon1, P. Vercellini3,4,5 and M. Candiani2 http://humupd.oxfordjournals.org/content/20/2/217.long

Drawing showing the ovarian damage caused by toxic factors in the endometriotic cyst AM Sanchez et al. Human Reproduction Update 2014

Drawing showing the ovarian damage caused by toxic factors in the endometriotic cyst
AM Sanchez et al.
Human Reproduction Update 2014

Antral follical count as a predictor of ovarian responsiveness in women with endometriosis or with a history of surgery for endometriosis

A vaginal ultrasound scan showing an ovary with an endometrioma. no other small follicles can be seen

A vaginal ultrasound scan showing an ovary with an endometrioma. no other small follicles can be seen

By I.Soussis MD

Antral follicle count AFC, has proven to be one of the most reliable predictors of ovarian response to the drug stimulation during IVF treatment. It refers to the number of small follicles counted at the ovary prior to starting the stimulation.

In 2015 Benaglia et al. researched AFC as a predictor in 83 women undergoing IVF due to endometriosis. These women had undergone surgery in the past for the removal of endometriosis(chocolate cyst) or had a cyst during their IVF attempt.

The ovaries were divided into four groups:

1-Ovaries without previous surgery and without endometriomas(42)

2-Ovaries without previous surgery, with endometriomas(46)

3-Ovaries with previous surgery without endometriomas(55)

4-Ovaries with previous surgery, with endometriomas(23)

The ovaries with surgery(78) and those with endometriomas(69) were analyzed statistically. The AFC was also investigated to see if it could predict poor ovarian stimulation (2 or less oocytes per stimulation) as well as hyperstimulation(7 or more oocytes per stimulation).

It was found that this predictor was prognostically useful, not only in ovaries with endometriomas but also in those without endometriomas and in those that had undergone surgery for endometriomas.

The most useful predictors of ovarian response and IVF success is the combination of the woman’s age, the antral follicle count and the levels of the hormones FSH and AMH.

Fertil Steril. 2015 Apr 29. pii: S0015-0282(15)00218-6. doi: 10.1016/j.fertnstert.2015.03.013. [Epub ahead of print]

Antral follicle count as a predictor of ovarian responsiveness in women with endometriomas or with a history of surgery for endometriomas.

Benaglia L1, Candotti G2, Busnelli A3, Paffoni A2, Vercellini P3, Somigliana E3.

Men living with endometriosis: insights and experiences of male partners, living with women with endometriosis

Image courtesy of holohololand at FreeDigitalPhotos.net

Image courtesy of holohololand at FreeDigitalPhotos.net

By I.Soussis MD

Hudson et al. from the UK, presented an interesting study at the latest ESHRE conference, held in Lisbon Portugal in June 2015.

The main question was: How do partners of women with endometriosis perceive the disorder and how do they help their wives/partners to deal with their symptoms and to seek medical help?

Endometriosis is a chronic gynaecological condition(disorder), affecting 5-15% of women, during their reproductive age.  The symptoms include painful menstruation, painful intercourse, tiredness, chronic pelvic pain and heavy periods.  Furthermore, 40% of visits to  fertility clinics are due to endometriosis.

Many studies show the negative effect endometriosis has on social and marital relations, as well as the help that the male partner provides.  However, most of these studies focus on the women’s experiences.

In this study “Endopart UK”, 22 heterosexual couples were interviewed.  The inclusion criteria were, a laparoscopic diagnosis of endometriosis and the cohabitation of the couple.  Both men and women were interviewed separately.

It was found that the impact endometriosis had on the daily lives of the men and on their feelings was impressive.

Every long term disorder affects the healthy partner, but endometriosis more than any other, because it affects the reproduction and sex life of the couple.

The partners took an active role during doctor’s appointments and helped their female partners to choose the right treatment. Their support during the implementation of the treatment was significant.

In the future, the treatment should not just focus on the woman, but should take into account the effect that endometriosis and its treatment have on the quality of the couple’s life and also that of the male partner.

ESHRE 2015, O-080: Men living with endometriosis:perceptions and experiences of male partners of women with the condition. N. Hudson, L.Culley, H. Mitchell, C.Law, E. Denny, N. Raine-Fenning

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