Procedia - Social and Behavioral Sciences 33 (2012) 213 – 217

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1877-0428 © 2012 Published by Elsevier B.V. Selection and/or peer-review under responsibility of PSIWORLD2011doi:10.1016/j.sbspro.2012.01.114

ProcediaSocial and Behavioral Sciences Procedia - Social and Behavioral Sciences 00 (2011) 000–000

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Genetic counselling in reproductive disorders Georgeta Camelia Cozarua, cr mioara Ionela Butnariub, Eusebiu Vlad

Gorduzab*

a“Andrei aguna” University, Constanta, Romania b“Gr. T. Popa” University of Medicine and Pharmacy Iasi, Medical Genetics Department, 700115, Iasi, Romania

Abstract

Reproductive disorders are an important medical problem, affecting 10-15% of couples of reproductive age. Theirs causes include: genetic, anatomical, endocrine, infectious or psychogenic factors. The main genetic factors in human reproductive disorders are the chromosome abnormalities, implied in >50% of early abortions and 5% of stillbirth. Our goal was to give genetic counselling of couples with reproductive disorders in order to identify genetic causes for the granting of proper counselling and to provide necessary support to reduce the psychological impact of genetic diagnosis of infertility and for this one is necessary to a multidisciplinary approach. © 2011 Published by Elsevier Ltd. Selection and peer-review under responsibility of PSIWORLD 2011

Keywords: Infertility; Genetic counselling; Recurrence risk; Psychological impact

1. Introduction

Reproductive disorders (RD) - primary sterility and infertility - are an important component of human diseases, affecting 10-15% of couples. Primary infertility (SP) is generated by the inability of an individual to form gametes or the inability of a couple to conceive. Infertility occurs in conditions in which the pregnancies end with recurrent miscarriages (ASR) or birth of a child with multiple congenital anomalies. RD affects both sexes and can be produced by feminine, masculine or couple factors (Schorge et al., 2008). According to the American Society for Reproductive Medicine (2006), the human RD are produced by different causes: masculine (25%) feminine (49%) or no known cause (26%). In general, the RD may be caused by endocrine, anatomic, infectious, immunological or genetic factors (Gorduza et al., 2003). The genetic factors, mainly a complete or partial aneuploidy, produce 50-60% of the early ASR in

*Corresponding author. Eusebiu Vlad Gorduza Tel.: +40-726-307328 E-mail address: vgord@mail.com.

© 2012 Published by Elsevier B.V. Selection and/or peer-review under responsibility of PSIWORLD2011

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the first quarter of pregnancy, about 1/3 of ASR in the second quarter of pregnancy and 5% of intrauterine deaths. Unlike full aneuploidy, usually caused by a nondisjunction in maternal meiosis, partial aneuploidy are the result of meiotic malsegregation of the derivative chromosomes given that one parent is a carrier of a balanced chromosomal abnormality (ACOG committee Opinion, 2007, Cunningham et al., 2010, Gorduza et al., 2011, Korteweg et al., 2008).

Genetic counseling is a communication process, provided premarital or postmarital, correlated with human problems generated by the genetic illness in the family. In this process, the geneticist establish the diagnosis and the importance of genetic factors, determines the risk of recurrence, discuss the reproductive options, ensures an adequate psychological support imposes by the impact of disease. Given that infertility is often associated with unbalanced chromosome abnormality, and sometimes one member of the couple have a balanced chromosome abnormality, the karyotype is required, thereby determining risk of recurrence that can vary from insignificant (<0.1%) to total (100%) (Gorduza, 2007).

The RD is experienced as a stressful situation by individuals and couples all around the world, and can include societal repercussions and personal suffering. While most couples are able to integrate the reality of infertility into their identity, the culmination of losses including personal genetic diagnosis, perinatal losses, and/or birth of an affected child may simply be too much (Burns, 1999). During the medical diagnostic test, couples need to wait the results of their investigation and this period is marked by a state of uncertainty associated with elevations in psychological distress (Broadstock et al., 2000; Esplen et al., 2001). For this reason, they may decline genetic testing of their condition, concerning stigma and insurance and feeling unable to emotionally deal with a positive genetic test result (Decruyenaere et al., 1997; Codori et al. 1999). Furthermore, denial, avoidance, and ambivalence can leave infertile couples ill-prepared or ill-equipped to cope with any losses precipitated by genetic screening or diagnosis. The genetic testing cause’s significant distress varies in principal according to: 1) test results; 2) clinically aspects of disease; 3) uncertainty remaining after testing; and 4) personal factors such as optimism, perceived risk, and beliefs (Baram, Friedman, Zakowski, 1997). To combat this distress, it is important to assist patients in the acknowledgment and discussion of negative feelings and defensive reactions in order to increase their awareness of the impact of their emotions on risk perception and decision-making (Kash and Lerman, 1998; Codori et al, 1999). After Decruyenaere, (1997), in an outline of psychotherapeutic interventions for infertile patients with genetic disorders, patients should be encouraged to reflect on the personal value and importance of having children and the strength of his/her personal reproductive drive. Patients should also be encouraged to: 1) improve the acquisition of information; 2) become more aware of the cognitive mechanisms and psychological defenses influencing their risk perception; 3) to be cognizant of possible framing effects when presented with genetic risks by using more than one way to understand the genetic risk information and 4) spend enough time on information processing (Frets and Neirmeiher, 1995). The purpose of this retrospective study was to identify the prevalence of chromosomal abnormalities in couples with RD in conjunction with the establishment the particularities of genetic counseling which would reduce the psychological impact on members of couple while the chromosome analysis confirmed a chromosome abnormality in one of the individuals.

2. Material and method

During January 2000 - December 2009 were evaluated, in the Genetics Center of Jassy, 229 couples with reproductive disorders include: recurrent miscarriages (ASR) - 149 couples (65.06%) and couple’s sterility (ST) - 80 couples (34.93%). For each couple with RD was performed the karyotype using a G banding, aiming to detect numerical or structural chromosomal abnormalities. The chromosomal analysis, based on a short-term culture of stimulated T lymphocytes was performed according to the technique Moorhead (Moorhead et al., 1960) and includes several steps: collection of peripheral blood on sodium

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heparin, putting blood in culture (culture medium RPMI 1640 supplemented with fetal calf serum and glutamine) treatment with a hypotonic solution, fixation, dropping on the slide, G banding and microscopic examination. For each case were analyzed a minimum of 16 metaphases. In cases where abnormalities were detected, the number of cells analyzed was increased to 32, 64 or even 96.

3. Results

In the case of 33 couples (14.41%) was detected a chromosomal abnormality in one of partners: 20 abnormalities in couples with ST (25% of these couples) and 13 abnormalities in couples with ST (8.72% of these couples). In 15 cases (6.55%) the anomaly was observed in women and in 18 cases (7.86%) in men. In 13 (8.72%) of the 149 couples with ASR, a chromosomal abnormality was detected, 8 (61.53%) of which are present in women. The most common abnormalities detected were inversion (6 cases – 2 cases with inversion on chromosome 9, 2 cases with inversion on chromosome 1, 1 case with inversion on chromosome 10, and 1 case with inversion on chromosome 15), followed by gonosomal aneuplody (X monosomy mosaicism - 4 cases). Also, we identified a balanced reciprocal translocation t(4;7), a balanced Robertsonian translocation rob(13q;14q) and an insertion ins(5;4).

In couples with ST were found 20 cases (25%) with chromosomal abnormalities, their frequency is almost twice higher in men (13 cases - 65%) than women (7 cases - 35%). The most common abnormalities detected in these cases were aneuploidy (8 cases - 40%): 47, XXY (6 cases) and X monosomy mosaicism (2 cases) followed by inversion (4 cases with inversion on chromosome 9 and 2 cases with inversion on chromosome 16). Also we detected a partial X monosomy by structural abnormalities of X chromosome (isochromosome and deletion) in 4 cases and 2 male patients with sexual inversion (karyotype 46,XX).

4. Discussions

The prevalence of detected chromosomal abnormalities in couples with RD included in this study was higher (14.41%) than that cited in other similar studies: 8.9% - Pal et al. (2009), 9.04% - Nazmy et al. (2008), 5.53% - Espinoza et al. (2008) and 1.97% Clementine et al (2005). The chromosomal rearrangements were detected in 57.57% of couples with abnormal karyotype being represented mainly by inversion (12 cases). Among numerical abnormalities the most common were X monosomy (homogeneous or mosaicism) - 6 cases (in women) and trisomy XXY - 6 case (in men). In most cases, the abnormalities were present in men (18 cases - 54.54% of the abnormalities) were similar to those obtained by other researchers (Clementine et al., 2005, Espinoza et al., 2008). Among structural chromosomal abnormalities, the balanced inversions were most common - 12 cases (5.24% of couples), and half of which are represented by pericentric inversion of chromosome 9 (2.62% of couples). However, the detection of such inversion complicates the genetic counseling while their prevalence in the general population is similar (1-3%). In addition, the involvement of pericentric inversions of chromosome 9 - inv(9)(p11q12) and inv(9)(p11q13) - in producing RD is controversial, given that indicate that these abnormalities can be considered a human chromosome polymorphism. Thus, are cited many familial cases with inv(9) where the reproductive potential of the carriers was not disturbed in any way (Mozdarani et al., 2007, Rao et al., 2006).

Compared to other abnormalities, our study allowed the identification of only 3 balanced chromosomal abnormalities (9.09% of couples with abnormal karyotype): 1 balanced reciprocal translocation, 1 Robertsonian translocation and 1 insertion. These abnormalities complicate the process of genetic counseling, each anomaly being associated with a specific risk of recurrence in future pregnancies (all abnormalities were found in couples with ASR). In the case of translocation t(4,7) the theoretical risk of

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having another affected foetus (that present partial 4 trisomy associated with partial 7 monosomy or vice versa) and the pregnancy ending by miscarriage is 50%. A similar situation occurs in men with insertion ins(4,5), which can form two types of abnormal products of conception: with partial trisomy 4 or partial monosomy 4. Instead, the carrier of Robertsonian translocation trob(13q,14q) can form six types of offspring of which 3 (with 14 trisomy, 14 monosomy, and 13 monosomy) are certainly non-viable, and the fourth, with trisomy 13, is also often eliminated by a miscarriage.

The presence of a gonosomal aneuplody or a structural abnormality of X chromosome has generated a reproductive disorder in 10 women and 6 men, the most common being X monosomy mosaicism (in women) and XXY trisomy (in men). This is not surprising, because numerous studies have indicated that one of the causes of habitual miscarriage would be the existence of a X monosomy cell line in woman. On the other hand, the XXY trisomy does not cause always a Klinefelter syndrome’s phenotype, and the only manifestation of abnormality is a primary and permanent male sterility. At two of the men with ST and azoospermia was identified a syndrome of sexual inversion (male 46,XX), caused by SRY gene’s translocation from the short arm of Y chromosome to short arm of X chromosome during paternal meiosis (Orozco et al., 1994, Ward, 2000).

Genetic counseling and testing can provide to the infertile couple opportunity to gain an explanation or greater understanding of the losses even though it carries with it the potential for genetic diagnosis or information that may be disturbing. From our experience, for many infertile couples, decisions to proceed with genetic testing or counseling are influenced by past infertility experiences, medical indications and acceptance of a genetic component to their infertility. Since the first meeting with the couple, genetic counselor may involve discussions concerning clinical aspects of a disease or presenting problem, family anamnesis, exploration of religious or personal ethics, reproductive goals, feasible medical treatments, and acceptability of prenatal genetic testing. Because a diagnosis of a genetic disorder can precipitate a crisis in the individual and endanger the stability of the marriage, genetic counselor needs to assess the emotional response, reactivity, and receptivity of the individuals, their response as individuals and as a couple. In all couples investigated we identified typical psychological reactions that include depression, anger, and frustration. Even after we provide all explanations and information about chromosomal abnormalities detected and their implication, what are the opportunities to reduce the recurrence risk for having problems to the next pregnancy, we observed persistent of emotional reactions and high tensions in the couple or individual. In all these situations we recommended psychologically counseling to manage their acute distress and anxiety.

5. Conclusions

In conclusion, the results of our the retrospective study, consistent with the literature, highlights the major role they have chromosomal abnormalities in production of human RD, while stressing the importance of chromosomal analysis for etiologic diagnosis, management and genetic counselling given to these couples. Thus, the karyotype should be an important step in the evaluation of patients with RD, especially in cases where recourse to assisted reproduction techniques.

We observed that couples with RD, who request a genetic consultation, often experience the distressing emotions and after notification of a possible genetic cause, typical reactions include depression, anger, and frustration. Also, we noted that it is essential pre-test genetic counseling for adequate training of persons to be tested and also post-test counseling, with proper explanation of implications of their results. It is very important to detect early the psychosocial problems and difficulties that present barriers to the fertility of the couple and may lead to negative consequences of treatment. Thus, it is necessary to collaborate with clinically psychologists, to imply them to support and help during emotional crisis occurring in the context of the treatment and counseling with respect to stress

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management. We believe that requiring a multidisciplinary approach to reproductive genetic issues is one that includes gynecology, endocrinology, medical genetics (for testing and genetic counselling), mental health and reproductive nursing.

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