Oct 17 2011 02:00 AM | Rick in Personal Reflections
A poll at IVF.ca asked members "who did you tell about infertility?". Of the mostly female respondents, 67% told a select few or none at all. 33% openly shared their situation with many people.
A sampling of issues/comments from the more private group (67%):
- Infertility/Family planning is a private matter.
- To stay away from unsolicited advice and opinions from people who have never experience infertility.
- Not wanting to be burdened with public expectations or questions throughout their treatments.
- To comply with the wishes of their partner.
- Concerned people will treat them with pity.
- Felt public failure would add undue pressure and stress.
- Expect some family members would react in a negative fashion or feel hurt by the news.
- Fear of workplace discrimination, concerned that an employer will overlook a hiring or promotional opportunity if their family planning goal is known.
- Not needing the support of others.
Unlike most other medical conditions, infertility is usually a shared condition with the patients surrounded by a diverse and sometimes complex set of relationships.
"My Mother-in-law made comments like she doesn't believe in ART procedures and only desperate people do that. I felt like strangling her at the time. She always assumes that her son is perfect and in perfect she means that he has no fertility problem. I know DH (husband) isn't comfortable about this to share with is family so all they know is that we have problems but don't know why. Even though he is diagnosed with Male Factor, we are together so this affects me just as much."
Despite a ratio of approximately 1 in 6 couples who experience difficulty trying to conceive, infertility remains a relatively silent medical condition.
Oct 10 2011 02:00 AM | Rick in Personal Reflections
In 2008, my husband and I had been trying to conceive for about 9 months when I sought info from another site with a message board. It frustrated me to be there because it was full of women who were complaining after TTC for a month or two and I could't relate because I felt like our nine months was forever! There was another member on those boards who suggested I take a look at ivf.ca - her screen name is DesignerBug.
For a few months, I would just dip my toes in the water of ivf.ca - I thought "I don't belong there, I haven't been through what those women have been through and we're not doing IVF". I was wrong. In Jan 2009 we did our first round of IVF and I dove in the deep end of ivf.ca through the 'New On The Block' thread, started by my good Australian friend, Edie.
I had finally found home in a group of women from all over the world. I found women I could relate to, be completely honest with and lean on when I needed to but also offer support when they needed it and I could help. This site offered so much and I wouldn't have made it through the past few years without it and I certainly wouldn't be where I am today without it but for a much different reason than you would think.
Our first IVF attempt in Jan/Feb 2009 failed - we transferred 3 great looking embryos but none of them took and we got a BFN. I turned to ivf.ca to work through my feelings and to help build up the courage to try again. And we did - in May/June 2009 we made our second attempt with IVF. Our second attempt resulted in a BFP and it was celebrated it seemed as much by my friends on ivf.ca as my own family. I felt like I had a whole room full of people cheering us on as we went to our 13 week ultrasound, anticipating seeing our bouncing baby on the screen. But that exciting day turned into one of the worst of my life when I heard those words I'll never forget "I'm sorry, I have no good news for you today". Our baby had died about 3 weeks earlier, a missed miscarriage.
I was enveloped in sympathy, empathy and shoulders to cry on here on ivf.ca. It was the worst time in my life but I was completely supported and was able to work through that horrible time without judgement and I came through it as a whole person - a different person but whole.
After the shock of our miscarriage, I didn't know which way to turn. I explored every possible path to our baby - donor eggs, surrogate, adoption, all of it and all right here on ivf.ca. Other members shared their stories, answered my questions, pointed out when I was spinning myself in circles (thank you GoodFortune!) and generally held my hand through all of it.
In Jan 2010, we had decided to adopt. We just couldn't do IVF anymore for many reasons. Once again, ivf.ca was there for me with a whole section of women who were going through the adoption process or had adopted. And even though it seemed like I didn't really fit into the general areas of ivf.ca, I still found members who could relate. Who had been through failed attempts, miscarriages and worse, long waits that I could never have imagined in 2008. So for a year, I stuck around even though it seemed our journey was stalled (adoption in NS is a painfully slow process).
In Jan 2011, our story got really interesting. We were getting ready to leave on a trip south when I got a PM from a member I didn't recall ever 'meeting' on ivf.ca. She said she had read that my husband and I were planning to adopt but she wondered if we had considered donor embryos. At first I thought, "it's really nice of her to contact me but why does she think I haven't already explored every option?". I replied and thanked her for her input but her second message to me really astounded me. She and her husband had done IVF two years earlier and had boy/girl twins who were about to turn 2 and they had 9 embryos leftover. If we wanted them, they wanted us to have them!
Because of ivf.ca, this wonderful woman had felt like she had gotten to know me through my blog and my posts and she felt comfortable enough to offer this amazing gift to us! The feeling of being chosen without ever knowing we were being considered is indescribable. The idea that someone would make this offer to us was unfathomable. But there it was.
Over the next few months, we talked and worked out all the details and in June 2011, I travelled to Calgary and as further proof to the strength of the relationships developed on this site, I stayed with another member who I had never met in person but felt like I had known for years (thank you babatime and your amazing family for opening your home to me). On June 8, 2011, I had 2 gorgeous embryos transferred to my uterus. I even had the opportunity to meet our donors and their two beautiful children the day before.
On Father's Day, I took a home pregnancy test and when it came up positive, my husband and I just laid in bed grinning at each other. It worked! I was pregnant!
As I write this, I have just passed the halfway mark in my pregnancy. Some would say I am halfway to meeting my son but this journey started four years ago and we passed the halfway mark quite sometime ago without ever realizing it. It is Thanksgiving weekend and I have a list as long as my arm of what and who I am grateful for. Very close to the top of that list is Rick, the founder and keeper of ivf.ca and all the members who have made this site what it is - home, a refuge, and the place that made our miracle happen.
I am blessed in so many ways and becoming a part of ivf.ca changed my life in a way I could never have imagined when I was dipping my toes in the water.
It is said that it takes an entire village to raise a child, well, sometimes it takes a whole village just to create one. IVF.ca is part of that village for our family. I honestly don’t know if we’d be where we are today without the support and information I gained from this online community.
When we learned that my egg supply was rapidly diminishing at the age of 32, and for reasons that remain unexplained we had not had success with surgery, oral ovulation medications, or multiple IUI’s with injectable stimulation. We turned our hope to IVF to help us find the golden egg and conceive a much wanted a child. After two attempts at IVF cycles had to be cancelled due to a poor response to stimulation. Our RE suggested that with the last attempt we would push forward to egg retrieval no matter how few eggs there were. I started the cycle with 4 antral follicles (about 1/5 of the normal amount for my age), and just 3 of those responded to the maximum dose of medication. Quality over quantity was our mantra. There were just 2 mature eggs on the retrieval day, and to everyone’s surprise both fertilized and we ended up with two great quality embryos to transfer on the 3rd day. Two weeks later we got the call we’d waited for 3 years -the pregnancy test was positive. We expecting our miracle IVF baby Dec 31st 2011. We are so grateful and so very lucky to have beaten the odds.
There were so many times I was so discouraged I wanted to pack it in, but I credit the support and advice I received along the way for helping me keep perspective and persistence on this crazy journey. I have made some real life friendships and connections with women who I’ve met on IVF.ca and want to be able to give back to this community in whatever way I can.
This entry describes the personal journey of IVF.ca founder, as written by a team of reproductive and scientists lead by Dr Sai Ma, University of British Columbia. It was published in the July 2003 edition of "Human Reproduction". It is reproduced here with the consent of Dr Ma.
ICSI and the transmission of X-autosomal translocation: a three-generation evaluation of X;20 translocation: Case report
Sai Ma1,3, Basil Ho Yuen1, Maria Penaherrera2, David Koehn2, Larry Ness1 and Wendy Robinson2
1 Department of Obstetrics and Gynecology and 2 Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
3 To whom correspondence should be addressed. e-mail: firstname.lastname@example.org
Published reports show that male carriers of an X-autosome translocation, which is either inherited from their mother or is de novo, are generally sterile, regardless of the position of the breakpoint in the X chromosome. We report a three-generation propagation of such a translocation in a family with a case of male factorinfertility. Due to the condition of severe oligozoospermia, the proband and his wife underwent ICSI, which resulted in the birth of a normal healthy female. Cytogenetic (chromosome) analyses and X-chromosome inactivation (XCI) assays were done on the family. The cytogenetic analysis of the proband, a man with severe oligozoospermia, revealed an X-autosomal translocation, 46,Y,t(X;20)(q10;q10), which was inherited from his mother. His brother had the same translocation. Amniocentesis and post-natal umbilical cord analyses revealed that the female infant carried the same translocation as her father. XCI studies showed highlyskewed inactivation of the normal X chromosome in the female infant, her paternal grandmother, and her mother who had a normal karyotype. In contrast to the data from the literature, our study suggests that men with a certain type of X-autosomal translocation could conceive children through ICSI in conditions in which a few spermatogonia are able to complete meiosis II. The literature involving X-autosomal translocation in males is also reviewed and the importance of the study of X-chromosomal inactivation in female infants discussed.
Key words: intracytoplasmic sperm injection (ICSI)/male infertility/X-autosomal translocation/X chromosome inactivation
1) with normal sized testes. His height was 183 cm and weight was 84 kg. The presence of severe oligozoospermia was established by means of several semen analyses. Serum gonadotrophins and testosterone were normal. He has had an ongoing history of infertility for 11 years. His only brother also has a long history of infertility, but managed to father two phenotypically normal daughters after 7 years of infertility. Neither semen analysis from his brother, nor paternity testing and karyotypes of his two daughters were available. The age of the proband’s mother at the birth of her sons was 35 and 42 years old respectively, and she experienced menopause at the age of 48. The female partner had no evidence of tubal, ovulatory or pelvic infertility factors.Apart from the infertility, no obvious abnormalities were present in his wife, himself or any other family members.
Figure 1. Pedigree of a familial translocation. Dotted circles represent balanced carriers of the translocation. The arrow indicates the proband patient.
The couple underwent IVF combined with ICSI for the treatment of male factor infertility. A standard luteal phase ‘long protocol’, of controlled ovarian stimulation using a GnRH agonist and recombinant FSH with intravaginal progesterone as luteal support, was undertaken in the female partner. Of the 20 oocytes retrieved, 16 metaphase II oocytes were identified by the presence of a single polar body. Only a few sperm (~50) were found after concentration of the semen sample into small pellets. Motile sperm were selected from the concentrated pellets and then transferred to the polyvinylpyrrolidone (PVP) solution. The detailed ICSI procedures have been described previously (Ma and Ho Yuen, 2000).
Somatic chromosome studies
Chromosome analysis of peripheral blood was performed for the proband, his wife, his brother and his parents. Umbilical cord blood was used for the chromosomal analysis of the newborn baby. Primary cultures were established and metaphase chromosomes were harvested using standard methods. In addition, genetic counselling and prenatal diagnosis for chromosomal analysis were offered to the proband couple. Chromosomal banding was performed by the trypsin–Giemsa method. A detailed protocol is provided in Lamet al. (2001).
X-Chromosome inactivation (XCI) studies
DNA was extracted from cord blood using standard techniques. An assay to examine XCI status requires a means of distinguishing the active from inactive X chromosome as well as a polymorphism to distinguish between the two chromosomes. This is usually accomplished by analysis of an expressed polymorphism or by determining the methylation status of CpG dinucleotides near the polymorphism. In the present study, XCI was tested predominantly by methylation analysis at the androgen receptor gene (AR), the fragile X mental retardation gene (FMR1) and DXS6673E. DNA was digested with HpaII, a methylation-sensitive restrictionenzyme, and both digested DNA and control undigested DNA were amplified by PCR with the respective primers. Methylated DNA was not cut by HpaII and was therefore amplified, whereas unmethylated alleles were digested and were not amplified. Non-random XCI was revealed by a difference in quantative intensity of the two alleles. The details of the method and results on placental XCI of this case have been described previously (Peñaherrera et al., 2003). This study was conducted with the approval of the Clinical Ethics Board at the University of British Columbia and included informed consent from all participants in the study.
2 and 3). The proband’s mother and brother were also found to carry the same translocation. The proband’s wife had a normal karyotype. The results of the amniocentesis showed that the fetus had the same translocation as the father. The post-natal umbilical cord study also showed the same result.
Figure 2. Proband’s karyotype 46,Y,t(X;20)(q10;q10). The arrows indicate the chromosomes with the translocation.
Figure 3. Chromosomes 20 and X of the child, her father (proband) and paternal grandmother.
Determination of X inactivation ratios
Methylation analysis at the AR and FMR1 locus demonstrated a completely skewed X inactivation pattern in post-natal cord blood from the female infant. A highly skewed X inactivation ratio was also observed in her mother, who did not carry the balanced translocation (Table I). Based on the AR assay, the female infant’s mother showed preferential inactivation of the same allele that was inactivated preferentially in her daughter. For FMR1, however, the mother was also skewed, but towards the inactivation of a different allele from that transmitted to her daughter. The mother was uninformative for marker DXS6673E (Table I). For the paternal grandmother, who was also a carrier of the translocation, the AR assay showed highly skewed XCI with preferential inactivation of the normal X chromosome (represented by allele, the same allele that was inactivated in the child, but was uninformative for both FMR1 and DSX6673E.
View this table Table I. Percentage of XCI in cord blood, and in maternal and paternal grandmother’s blood
The clinical phenotype in patients who have a translocation involving the X chromosome and an autosomal chromosome frequently differ from those cases where the translocation involves two autosomes (Madan, 1983; Kalz-Füller et al., 1999). The phenotypic consequence, in terms of reproductive fitness, of an X-autosome translocation in our study family is consistent with known consequences of balanced X-autosomal translocation in carriers, i.e. all three carriers in this family had a normal phenotype, with proven fertility in the proband’s mother, and infertility in the male proband (Madan, 1983>; Kalz-Füller et al., 1999). This case is unique as it is, to our knowledge, the first reported instance where an X-autosome translocation was transmitted from a male to his offspring through ICSI. It seems likely that meiosis proceeded normally in at least some cells during spermatogenesis, in order to generate balanced haploid gametes.
Translocations involving a portion of the X chromosome have a profound impact on spermatogenesis, as indicated by the failure of most spermatocytes to enter into meiosis (Jamieson et al., 1996). In certain cases, spermatogenesis can proceed to the formation of elongated spermatids, but the process is remarkablyinefficient, as indicated by the presence of a few sperm. Up to now, only two cases (excluding ours) produced two children, while most of the other reported cases involving X-autosomal translocation presented with azoospermia (Table II). Our case not only presented with severe oligozoospermia in the proband, but also included three other familial carriers, including the proband’s brother.
Table II. Human reciprocal X-autosome translocations associated with infertility in males
Review of 26 males (Table II) with X-autosomal translocation did not show marked preference for involvement of a specific autosome, but it appears that the breakpoint occurs more often in the critical region of Xq13–q26 (17 out of 26 cases). However, the fact that the breakpoints in nine cases were distributedoutside the critical region suggests that, unlike female carriers who have reduced fertility predominantly associated with the breakpoint in Xq13–q26, the male carriers are invariably sterile, regardless of the position of the breakpoint on the X chromosome (Kalz-Füller et al., 1999). The breakpoint in our case involves the centromeric region in both the X chromosome and chromosome 20, followed by fusion of the two long arms and the two short arms. This balanced translocation may have fewer detrimental effects on spermatogenesis than other X chromosomal breakpoints, allowing a few spermatogonia to undergo meioticevents and consequently producing a few sperm with balanced translocation.
Because ICSI needs only one spermatozoon to fertilize an oocyte, most subfertile and infertile men, i.e. men with either very few sperm (extreme oligozoospermia) or no sperm (retrieval from testis) in the ejaculate, can now father a child (Ma et al., 2000; Silber, 2000). Our case illustrates this possibility of producing offspring from a patient with severe oligozoospermia by ICSI, and also demonstrates that germ cell maturation canexist in males with an X-autosome translocation with some sperm containing the balanced translocation. However, the risk of producing progeny with an unbalanced translocation also exists through ICSI. With the advent of ICSI, more cases with X-autosomal translocations are likely to be discovered and may produce offspring with balanced translocation in conditions where a few spermatogonia can complete meiosis II. Furthermore, with the development of microdissection testicular sperm extraction (TESE) (Silber, 2000), sperm or mature spermatids from some men with azoospermia and with X-autosomal translocation may be likely to be retrieved from the testis (Quack et al., 1988), and used for ICSI.
The risk of an aneuploid offspring for X-autosomal translocation carriers seems to be similar to that for reciprocal autosomal exchanges (i.e. it would depend on the autosome involved, the length of the translocated segments, the configuration at pachytene and the expected segregation) (Jalbert et al., 1980; Stene and Stengel-Rutkowsky, 1982). Moreover, the viability of the resulting imbalance could be favoured by a ‘selective’ inactivation. In this family, the infant and the paternal grandmother, who are both carriers of the balanced X;20 translocation, had skewed X-inactivation of the normal X chromosome, thus conforming to the normal X chromosome behaviour in X-autosomal translocations, i.e. the normal X in most female carriers is inactivated in order to keep a balanced dosage of expressed genes (Mattei et al., 1982). The normal phenotype in the females and fertility in the paternal grandmother of this family may be due to thetranslocation involving the entire short and long arm of the X chromosome, allowing the critical region for maintaining gonadal function to be uninterrupted.
In conclusion, our study confirms the transmission of an X-autosome translocation from mother to son. In contrast to the published data, the son transmitted the inherited translocation to his daughter, producing a three-generation X-autosome translocation, which can only result from ICSI under conditions in which a few spermatogonia can complete meiosis II. Since severely infertile males may have reciprocal translocations involving either the X and/or an autosomal chromosome, it is of clinical importance to determine to what degree skewed X-chromosomal inactivation is present in the resulting female newborns with X-autosomaltranslocation. This information can be used to predict the risk of an abnormal phenotype and presence of an X-linked disease in these newborns from ICSI so that the parents can be counselled accordingly.
We gratefully thank the family for donating the samples for this study, the clinical and laboratory staff of the University of British Columbia IVF Program in the Division of Reproductive Endocrinology and Infertility for their clinical work, and Mr Steven Tang for the help with preparation of the manuscript. This study was supported by The Hospital for Sick Children Foundation (grant no. XG 02-086).
This infertility journey is moving my life into a new direction. It has cast me out of my habitual comfort zone and into the wilderness. This journey has confronted me with questions that I haven't seriously considered for almost 20 years.
Who do I want to be and become in this lifetime?
Does my work define me?
What do I believe in; what is the source of my faith?
Am I the person now at almost 40 that I expected to be when I was 20?
What would I do differently if I could turn back the clock?
And although I didn't consider it at 20, who am I if I can't be a mother?
Sitting here tonight, I don't have answers to any of these questions. And don't expect that I will anytime soon. But I am thinking... As DB charmingly said, the hamster is running! For me, perhaps after sleeping a little too long!
It occurred to me today that the failure of my cycle may actually have been a blessing in this respect; if the pregnancy had been a healthy one, I might not have asked these questions. I probably wouldn't have written 8 or more journal entries over the last 7 days trying to better understand myself. I know that there would have been other questions; perhaps just as important, but maybe I am exactly where I am supposed to be right now.
I started seeing a therapist mid-stream during my last IVF cycle and have continued. Although we talk about IVF and the challenges of managing the cycle, mostly we talk about who I am now, how I got here, and where I would like to be tomorrow.
Last week, part of my homework was watching the movie North Country. If you haven't seen it, this is a fascinating movie about a woman whose life is full of drama. On the surface, she is part of a small group of women who are amongst the first women to work in a mine and who suffer gross sexual harassment. On a personal level, she is dealing with the legacy of personal abuse and betrayal. While I don't love all of her behaviors, I love the spirit this character shows in standing up for what is right and in encouraging community amongst women.
Over the last day or two on these blogs I have seen examples of this spirit. Mollygirl's passionately articulate political activism; DB's discussion about not letting worry dominate; Ceska's ode to butterflies. Dreaming's Life as a Girl hit a real cord and spoke so beautifully about the making of girls and women. I have also seen thoughtful reactions on the forums to articles in the press about infertility and IVF that fail to recognize our voices.
In my experience, women don't always easily form community. But I see it here and feel its embrace. Just as importantly, I find role models here and learn something each time I visit. Here are women who despite the hardship and fear inherent in this process strive to do the right thing, for themselves and for others. Women who in their own grief can extend a warm helping hand to others who come in pain and feeling broken.
The questions of who I am and who I want to become are complex - I am sure that I will grapple with them long after the beta on my next cycle has made itself known. This is a good thing; I want to live my short life consciously - even when it is painful. I know at least that the person I want to be is one who stands up for what is right.
I feel blessed to be able to contemplate these questions in this place full of role models and compassion, in a place were community thrives.