Mayer Rokitansky Kuster Houser syndrome: Psychosocial and Fertility Aspect

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Mayer Rokitansky Kuster Houser syndrome: Psychosocial and Fertility Aspect

https://doi.org/10.21203/rs.3.rs-4951796/v1

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Introduction: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is congenital disorder that affects the female reproductive system. MRKH syndrome is characterized by congenital aplasia of the uterus or utero-vaginal agenesis with normal ovaries and normal breast development. In MRKH syndrome females, the chromosome number is normal (46, XX). The MRKH patients suffer with primary amenorrhoea, sexual problems, and infertility along with depression. It is inherited in an autosomal dominant pattern with an incomplete degree of penetrance and variable expressivity in the patients in the family. The females patients also have to suffer psychosocial problems and mental trauma. The prevalence of MRKH syndrome is about 1 per 4500 female live births. MRKH syndrome can be either isolated (MRKH type I) or syndromic form (MRKH type II or MURCS association) which is associated withrenal, vertebral, and to a lesser extent with auditory and cardiac defects. MRKH type II or MURCS association is characterized by Müllerian duct aplasia, renal dysplasia, and cervical somite anomalies in the female patients.

Material and Methods: In our study, a total of 50 patients having MRKH syndrome were enrolled for clinical investigation. The detailed clinical history of the patients were observed and diagnosed the patients by evaluating the reports of USG, MRI, and other tests including biochemical tests. The all associated abnormalities of vital organs including kidney, liver, heart, and other associated organs were recorded for each patient. Chromosomal abnormalities like aneuploidy, breakage, and translocation were ruled out by karyotyping. In the females patients, levels of hormones like luteinizing hormone (LH), follicle-stimulating hormone (FSH), Tri-iodothyronine (T3), Thyroxine (T4), and thyroid stimulating hormone (TSH) were estimated from serum or plasma. All the detailed information and history required for fertility aspects were interrogated to patients and documented their future plans related to fertility.

Results: In this study, we enrolled a total of 50 MRKH female patients and studied their problems of psychosocial, sex, and infertility. Most of the cases (52%) of MRKH syndrome were diagnosed between the age of 18 to 22 years, while the age group of 14-18 years and 22-28 years were distributed with 20% and 28%, respectively. Prevalence of MRKH syndrome is higher 64% (32 cases) in rural location as compared to urban location 36% (18 patients). MRKH syndrome were diagnosed after marriage in 70% patients. The reason could be either hiding the clinical manifestations and symptoms that included the overlapping features of amenorrhoea (40 patients), infertility (30 patients), and sexual problems (35 patients). Out of 50 females, 30 patients were underwent surgery for McIndoe-Vaginoplasty. MRKH syndrome patients were counselled that resulted adoption of child in 5 couples (cases) and surrogacy in one case. In our study, 20 females were got married with a widower person who already have children.We also focused on the diagnosis the abnormalities in associated organs including renal, cardiac, skeletal, and auditory in female patients suffering with MRKH syndrome.

Conclusion : MRKH syndrome is a rare syndrome in females but causes many psychosocial and fertility problems in patients. The counselling plays an important role in females suffering with MRKH syndrome.

Sexual & Reproductive Medicine

Surgical Obstetrics & Gynecology

MRKH syndrome

Reproductive system

Infertility

Karyotyping

Hormones

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a birth defect of female reproductive system that is characterized by aplasia of the uterus and the upper part (2/3) of the vagina with normal development of secondary sexual characters including breast development. In MRKH patients, karyotype is normal (46, XX). MRKH syndrome is inherited in an autosomal dominant pattern with an incomplete degree of penetrance and variable expressivity in the patients. The prevalence of MRKH syndrome is about 1 per 4,000 to 5,000 live female births (Golombok et al., 2006). MRKH syndrome is a stressful clinical condition for a young patient. MRKH females have shown several health problems including psychological, social, medical, and fertility in young females (Rall et al., 2015). Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome refers to the congenital aplasia or severe hypoplasia of the structures those derive from the mullerian ducts such as upper vagina, uterus, and fallopian tubes. The patients have shown normal and functional ovaries with normal breast development. Furthermore, karyotyping is normal with 46, XX chromosomes in the females (Esfandiari et al., 2004).

MRKH syndrome is clinically diagnosed by utero-vaginal agenesis, but several other clinical variants or manifestations are also associated with patients. MRKH patients have shown either obstructed uterus or rudimentary horn with functional endometrium (Morcel et al., 2012; Raziel et al., 2006; Albers et al., 2012). In MRKH syndrome, primary amenorrhoea is also observed. Since, both ovaries are normal in the patients. Therefore, breast development is normal in the female patients. Most of the patients were shown by blind vagina (Mok-Lin et al., 2010; Davis et al., 2008). Though, some parents and guardians of the patients were hide the symptoms of young female patients and marry their daughter without disclosing the clinical and structural conditions of MRKH syndrome. After marriage, young females have to face so much mental trauma. Since, awareness about the MRKH syndrome is very less in people living in villages and rural areas. So, counselling is most important and helpful for patients and their family members to prevent the social and mental trauma (Nik-Zainal et al., 2011). So far, only few studies have been performed on the psycho-social problems in the Indian MRKH patients (Chandekar et al., 2017; Mohanty et al., 2017). Only a few number of studies are available that deals the counselling of fertility options available to MRKH syndrome patients. These patients were found emotionally upset because they lack the normal reproductive functions (Pompili et al., 2009).

MRKH patients exhibits a specific, unique, and abnormal clinical phenotypes of female reproductive organs, but patients have capability to carry a pregnancy, even in the obstructed uterus through ‘Zygote intra fallopian transfer (ZIFT)’ or ‘Gamete intrafallopian transfer (GIFT)’. Previously, several successful pregnancies have been reported in MRKH patients via ZIFT and GIFT. Before the emergence of advanced and powerful reproductive technologies, the fertility options and opportunities for child adoption were very limited for women with uterine agenesis or bilateral rudimentary horns. Although, presently both ‘gestational’ and ‘in vitro fertilization (IVF)’ are common procedures for surrogacy that allows MRKH females to carry a pregnancy with genetically related child (Wang et al., 2014).

In MRKH syndrome, there are two types of MRKH syndrome are diagnosed, either type I (isolated or non-syndromic) or type II (syndromic form). To confirm the types of MRKH syndrome, anatomical examination is required to diagnose and confirm the MRKH types (isolated or syndromic) in the patient. MRKH type I syndrome is recognized by complete uterus aplasia in the presence of two rudimentary horns linked by a peritoneal fold and normal fallopian tubes (Jones, 1988). However, type II MRKH syndrome (or MURCS a ssociation) is confirmed by uterine symmetric or asymmetric hypoplasia with aplasia in one of the two horns or a size difference between the two horn rudiments, coupled with tubar malformations such as hypoplasia or aplasia of one or the two tubes (Strubbe et al., 1994). The cases of type II or MURCS association were commonly associated with the abnormalities of kidney (unilateral agenesis, ectopia of kidneys or horse- shoe kidney), skeletal or vertebral (Klippel-Feil anomaly; fused vertebrae, mainly cervical; scoliosis), and hearing defects. The most frequent skeletal anomalies include malformations of the spine in 30–40% cases that mostly presented as Klippel–Feil anomaly or scoliosis. Syndromic form of type II MRKH syndrome is termed as Genital Renal Ear Syndrome (GRES). Type II MRKH syndrome is rarely associated with cardiac defects and digital anomalies, such as syndactyly and polydactyly (Bombard and Mousa, 2014). Altogether, associated upper urinary tract malformations are found in about 40% of cases with MRKH syndrome. Unilateral renal agenesis was observed in 23– 28% cases, while ectopia of kidney of either one or both kidneys and renal hypoplasia were diagnosed with 17% and 4% in MRKH cases, respectively. Horseshoe kidney and hydronephrosis were also observed in few cases of MRKH syndrome (Strubbe et al., 1994).

In the cases of MRKH syndrome, both patients as well as parents are needed for counselling. Counselling of patients about clinical and anatomical conditions leading to infertility problem is very important. Since, patient undergo so much psycho-social trauma because of a lot of reproductive problems arises that results to an absence of pregnancy condition. Due to absence of pregnancy, this mental trauma is tremendous in patients. Therefore, many women have to face divorce and depression in their marriage life (Sultan et al., 2009). Though, surrogacy is very costly procedure to become a parents or mother having genetically related child. Sometime, women having MRKH syndrome are forced to marry with a widower (man) who already having children. So far, only a few literatures are available that covers this psychosocial part in MRKH patients. Thus, hysterectomy could not be better option for settling this psychosocial problems until thorough counselling regarding potential fertility to the female patients. We recommend to guardians of female patients having vaginal and cervical agenesis with a midline uterus that the uterus remains in place at least until the young woman is > 18 years of age, at which time she can make an informed decision for her own reproductive future (Chandekar et al., 2017). In our study, we investigated the psychosocial problems faced by women having MRKH syndrome.

In the present study, a total of 50 patients suffering with MRKH syndrome were enrolled from Department of Obstetrics and Gynaecology, Institute of Medical Sciences (SS Hospital), Banaras Hindu University, Varanasi. Informed written consent was obtained from each female patient for this study. This is a retrospective study in which previously operated MRKH syndrome patients were included. Detail data of previously operated female patients was collected from Operation register. In this study, new patients were also enrolled from last two years. General, systemic and local examination were performed in the females. The detail history of female patients were recorded which was mainly included the history of menstrual and fertility. The important parameters such as age, socioeconomic status, rural or urban location, and education qualifications were also documented.

A questionnaire was filled and statistical analysis were performed. Briefly, questionnaire was included the following information; 1) First time visit and report to doctor by MRKH syndrome patient, 2) The main complains and problems of patients, 3) Marriage history including duration of marriage months or years i.e., when patients got married ?, 4) Why did patients or guardians hide the abnormal clinical symptoms of reproductive system ?, 5) Have patients or guardians got any information about MRKH syndrome from doctor ?, 6) What was the advice given to patients regarding fertility issues ?, 7) How many patient underwent surgery (McIndoe-Vaginoplasty) and how many patients used vaginal dilators. This study also evaluated the total number of patients those had marriage without informing her husband and his family before marriage. What was the outcome of marriage ? How many MRKH patients had divorced. What method they adopted for fertility problems such as surrogacy or adoption of a child.

In MRKH patients, clinical history of the patients were documented. MRKH patients were clinically diagnosed by USG, MRI, hormone levels, and other related biochemical tests. The all associated abnormalities of vital organs including kidney, liver, heart, and others vital organs were diagnosed. Chromosomal abnormalities (like, aneuploidy, breakage, and translocation) were ruled out by karyotyping from blood lymphocytes. In the MRKH females, levels of hormones like luteinizing hormone (LH), follicle-stimulating hormone (FSH), Tri-iodothyronine (T3), Thyroxine (T4), and thyroid stimulating hormone (TSH) were estimated from serum or plasma (Fraser et al., 1973; Carranza-Lira et al., 1999). All the detailed information and history required for fertility aspects were inquired from patients and noted their future plans related to fertility.

The results were observed and documented on the basis of several parameters (given in Table1 to 8). For example, MRKH syndrome was highly diagnosed (52%) in females with age between 18 to 22 years. However, age group females with 14–18 years and 22–28 years were distributed with 20% and 28%, respectively (Table 1).

Table 1

Age wise distribution of MRKH patients (N = 50) in the present study.
Age group of patients (years)	Number of Patients	Percentage (%)
14–18	10	20%
18–22	26	52%
22–28	14	28%
N = represents the number of patients

Out of 50 MRKH females, 32 females (64%) were observed from rural location, while urban location was included with 18 patients (36%) (Table 2).

Table 2

MRKH patients (N = 50) with distribution of locations (urban and rural)
Location	Number of Patients	Percentage (%)
Urban	18	36%
Rural	32	64%

Most of the patients (46%) were belong from family having low income, while middle family contributed average patient (34%) and least number of patients (10 or 20%) were by accounted by high income family (Table 3).

Table 3

Socio-economic status of MRKH female patients (N = 50)
Socio-economic status	Number of Patients	Percentage
Low income	23	46%
Middle income	17	34%
High income	10	20%

Out of 50 female patients, MRKH syndrome was observed in 70% females (35) after their marriage (Table 4). Though, 15 females were not married due to problems of abnormal reproductive system. Out of 15 unmarried females, 10 teenager girls without marriage, they have not attained 18 years of age.

Table 4

Status of marriage in MRKH syndrome (N = 50)
Status of marriage	Number of patients	Percentage of patients
Unmarried (due to age < 18 years in 10 girls)	15	30%
Married	35	70%

The main clinical conditions and problems in MRKH females were observed with overlapping features of amenorrhoea (40 cases), infertility (30 patients), and sexual problems (35 females) (Table 5). Additionally, depression was diagnosed in almost all patients (48 cases).

Table 5

Main complains or problems of MRKH patients (N = 50)
Clinical symptom/problems	Number of patients
Amenorrhoea	40
Infertility	30
Sexual problems	35
Depression	48

Out of 50 females, 30 patients were underwent surgery (McIndoe-Vaginoplasty) (Table 6). However, 15 patients were found without surgery (e.g., McIndoe-Vaginoplasty, dilators, etc.). Five patients had not received any treatment for caring of MRKH syndrome related problems.

Table 6

Surgery and treatment done in MRKH patients (N = 50)
Type of treatment	Number of patient	Percentage
McIndoe-Vaginoplasty (surgery)	30	60%
No surgery	15	30%
No treatment	5	10%

Table 7

Outcome of counselling of MRKH patients associated with infertility ( N = 35)
Treatment	Number of patients
Child adoption	5
Surrogacy	1
Uterus implantation	0
Females got married with a widower person who already have children	20
Couple does not want babies	6

Table 8

Outcome of marriage with women having MRKH syndrome (N = 35)
Outcome of marriage	Number of patients
Divorced after marriage	15
Happy without children	5
Adopted the child	5
Satisfied with marriage to a widower where already children are there	20

MRKH syndrome patients were counselled. Consequently, the patients or couple (herself and her husband) were adopted child in 5 cases and surrogacy in one case. Additionally, 20 females were got married with a widower person who already have children. Though, there are 6 couples (with MRKH females) do not want babies through either child adoption or surrogacy.

In Mayer-Rokitansky–Kuster–Hauser syndrome, aplasia of uterus and vagina have been observed. The secondary sexual characters including breast development, pubic hair as well as axillary hair are normal. In MRKH patients, chromosome number was normal (46, XX) that was confirmed by karyotype (Williams et al., 2017; Fedele et al., 2007). The main complain of the patient was primary amenorrhoea before marriage, while issues of sexual problems, infertility, and depression due to social and domestic violence with patients were observed after marriage. The frequency of MRKH syndrome is 1 per 4500 female births (Folch et al., 2000).

History of MRKH patients were documented. Clinical diagnosis and anatomical examination were performed by clinicians to identify the clinical manifestations and associated abnormalities of renal and skeletal systems. Other investigations were also required for the diagnosis of trans abdominal ultrasound (USG), Karyotype, hormonal profile including LH, FSH, prolactin,T3, T4, and TSH. In a few cases, hearing impairment and cardiac problem are associated in which audiogram and echocardiography are used to confirm the associated conditions.

In this study, MRKH syndrome was primarily diagnosed (52%) in females with age between 18 to 22 years. The prevalence of MRKH syndrome is more frequent in rural areas and in families with low income. The common clinical manifestations which may be overlapping in these patients were amenorrhoea (40 cases), infertility (30 patients), and sexual problems (35 females), and depression (48 cases). Moreover, 30 female patients were underwent surgery (McIndoe-Vaginoplasty). Counselling of patients were resulted into child adoption in 5 cases and surrogacy in one case. Eventually, 20 females were got married with a widower person who already have children.

Since, MRKH syndrome women suffer with depression and social stigma. Therefore, it is suggested and advised that counselling of patients and their guardians or family members (including husband, if female married) is very important for better life of patients having less or no mental trauma and depression. This study suggests that MRKH patients can be grouped together so that patients do not isolated from family and society, and also they can help to each other mentally or economically or both (Morcel et al., 2012). In the MRKH syndrome, sexual problems can be solved by treatment through creation of new vagina in female patients. This treatment is both surgical and non-surgical procedures. This treatment is commonly performed at time of 4 month before marriage. The female patients must have attained the age of 18 years with adult and mature status. McIndoe-Vaginoplasty is the surgical method used for creation of new vagina in the female patients. Non-surgical method includes vaginal dilators which slowly increase the length and diameter of vagina.

For MRKH syndrome, decision of marriage is very important part of life that affects the sexual and psychosocial problems of patients. Regarding marriage, the male partner (husband) and his family members should know about the sexual and infertility problems of the patient (female partner) before marriage. The hiding of this clinical conditions of patients leads to domestic violence, psychosocial problems and converted into separated or divorced life. In a few circumstances, female patient get marry to man in the families where children are not required from newly married women. For example, a person having already kids, but his wife has died. In the present study, counselling of female patients has been performed that is helpful to solve problems related to sex and fertility. Our counselling suggests to go for McIndoe-Vaginoplasty and child adoption. Both partners: male and female (or patient) can be choose an option of surrogacy, because ovaries are normal in female patients. If semen of male partner is normal, then they can be the genetic parents of genetically related child. In rare cases, parents can also prefer the adoption of child.

Mayer-Rokitansky–Kuster–Hauser syndrome is rare, having many psychosocial, sexual, and infertility problems. Our study suggests that proper counselling is required for female patient and their family members including her guardians as well as husband and his family members. We advise to the guardians of patients to decide the marriage of females or girls having MRKH syndrome carefully. In this study, we also counselled and explained to patients about details procedures of treatments and surgery. Prior to start these treatment and surgery, patient must be adult and could be psychologically and emotionally mature. Creation of neovagina could be a better option for patients that can be achieved by surgical (McIndoe-Vaginoplasty) and nonsurgical (dilators). After surgical treatment follow up is very important for patients. For long term success in the patient, importance of regular intercourse must be explained. Infertility problem should also be discussed with the married couple and their family members. They can choose one of two procedures with their own eggs and sperms, either in vitro fertilization (IVF) or surrogacy. Additionally, adoption of child is another option for patient or couple and their family.

The present study has been approved by ethical committee of Institute, IMS, BHU, Varanasi, India. The informed written consent was obtained from each patient and the parents/guardians, if the patient was under 18 years of age.

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The authors declare no competing interests.

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Mayer Rokitansky Kuster Houser syndrome: Psychosocial and Fertility Aspect

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