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Introducción: Desde su primera descripción en 1984 las indicaciones de donación de óvulos han ido aumentando, lo que ha provocado un incremento progresivo en el número de ciclos realizados a nivel mundial. Aunque esta técnica de reproducción garantiza una elevada tasa de embarazo en la receptora, los profesionales también se esfuerzan en convertir el tratamiento para la donante en un proceso sencillo y seguro. Durante los últimos diez años los antagonistas de la GnRH, por sus características farmacodinámicas, ha sido el fármaco utilizado para desarrollar protocolos de estimulaciones ováricas sencillos y seguros para las donantes de óvulos. Materiales: La presente tesis doctoral resume las conclusiones de dos artículos publicados recientemente (2010) sobre la utilización de antagonistas de GnRH en la estimulación ovárica de donantes de óvulos. Además se discuten las conclusiones de otros cuatro artículos (publicados en revistas científicas de impacto durante los años 2006 y 2009) estrechamente relacionados a los aquí publicados. Los objetivos de esta tesis son: 1. comparar la eficacia de protocolos de estimulación basados en antagonistas de GnRH en comparación con protocolos basados en agonistas de GnRH a través de una revisión sistemática de la literatura y meta-análisis. 2. ilustrar que los protocolos de estimulación basados en antagonistas de GnRH aumentan la seguridad de la estimulación ovárica para la donante a través de una eliminación completa del riesgo del síndrome de hiperestimulación ovárica (SHO). Resultados: 1. El meta-análisis de de ocho ensayos clínicos llevados al cabo en donantes de óvulos estimuladas con antagonistas de GnRH no han demostrado diferencia significativa en el número de ovocitos obtenidos y las tasas de embarazo evolutivos en las receptoras correspondientes en comparación con agonistas de GnRH. 2. El estudio observacional, prospectivo realizado en donantes de óvulos de alto riesgo ha demostrado la eliminación completa de SHO moderado/severo tras la descarga con bolo de agonista de GnRH. Además se discuten las conclusiones de cuatro otros estudios apoyando las conclusiones mencionados arriba. Conclusiones: En el contexto de la donación de óvulos los protocolos de estimulación ovárica basados en antagonistas de la GnRH son igual de eficaces que los protocolos con agonistas de la GnRH. La inducción final de la maduración ovocitaria se puede llevar a cabo satisfactoriamente con un bolo de agonista de GnRH en vez de hCG, lo que prácticamente elimina el riesgo de SHO moderado/severo. La utilización preferencial de este protocolo de estimulación ovárica es muy aconsejable porque permite un tratamiento más sencillo y aumenta considerablemente la seguridad de la estimulación ovárica en donantes de óvulos. / Background: Since its first description in 1984 the indications of oocyte donation (OD) has widened considerably which has led to a continuous increase in the number of OD treatment cycles performed worldwide. Although this treatment option secured the highest pregnancy rates for the recipients of donor oocytes increased efforts were also made to achieve safer and simpler treament protocols for the oocyte donor. During the last decade with the advent and increased use of the GnRH antagonists this new pharmacological agent was also explored in ovarian stimulation protocols specifically tailored for oocyte donors. Materials: The present doctoral thesis summarizes the findings of two recently published articles (2010) on the application of GnRH antagonists in the ovarian stimulation of oocyte donors. Furthermore the findings of another four strictly related articles (published in high-impact international journals between 2006 and 2009) are also discussed. The primary objectives were: 1. to compare efficiency of GnRH antagonist protocols in comparison with GnRH agonist-based protocols in the context of oocyte donation by means of a systematic review and meta-analysis and 2. to illustrate that GnRH antagonist protocols substantially increase the safety of ovarian stimulation for oocyte donors by reducing or even eliminating the incidence of moderate/severe ovarian hyperstimulation syndrome (OHSS). Results: 1. A meta-analysis of eight randomized clinical trials (RCTs) performed in oocyte donors undergoing stimulation with GnRH antagonists showed no significant difference in the number of retrieved oocytes or recipient ongoing pregnancy rate when compared with GnRH agonists. 2. A prospective, follow-up study of a group of high risk oocyte donors showed that early onset moderate/severe OHSS was completely eliminated after triggering with a GnRH agonist. Furthermore the findings of four studies supporting the above conclusions are also presented. Conclusions: In the context of oocyte donation the GnRH antagonist based ovarian stimulation protocols are equally efficient compared to down regulation by GnRH agonists. The induction of final oocyte maturation can be successfully achieved by a GnRH agonist instead of hCG which practically eliminates early-onset moderate/severe OHSS. The proposed ovarian stimulation protocol should be preferentially used because it permits the simplification and considerably increases the safety of ovarian stimulation for oocyte donors.

Background: An increasing number of couples turn to treatment with oocyte or sperm donation, but there is limited knowledge regarding the consequences of these treatments in a program using identifiable donors. Aim: The overall aim was to study information-sharing among heterosexual couples following identity-release gamete donation. A further aim was to study donors’ attitudes towards future contact with donation offspring. Methods: The four studies were part of The Swedish Study on Gamete Donation; a prospective, longitudinal study of donors and recipients of donated oocytes and sperm. Study I and II had a quantitative approach with recipients of donated oocytes or sperm participating through questionnaires at start of treatment, two months after the first treatment and when their child was 1-4 years old. Study III was a qualitative interview study with 30 parents following sperm donation with school-aged children. Study IV had a quantitative approach with oocyte and sperm donors participating through questionnaires 5-8 years post-donation. Results: Study I revealed that the recipients of donated gametes in general were open about their treatment with the people around them and supported disclosure to offspring regarding his/her genetic origin. Study II reported that most of those who became parents following donor conception intended to share information about the donation with their offspring and some had already started the information-sharing process with their young child. Study III described information sharing with the offspring to be a process of several levels, revealing various amounts of information about the way of conception. The parent was seen to be the owner of the process and moving the process forward with different aspects and the reactions of the offspring serving as driving or impeding forces of the process. Study IV reported that a majority of the gamete donors seem to have a positive or neutral attitude towards a future meeting with a donation offspring. Conclusion: The present thesis suggests that there is a trend towards more openness among recipients of donated gametes in Sweden. It also points out that most recipients and donors within the Swedish gamete donation programme acknowledge the child’s right to his/her genetic origin and have the best interest of the child in mind.

<p>Involuntary childlessness is a big problem around the world. One way to solve the problem is to receive oocytes or semen from a donor. In Sweden, semen donation has been regulated by law since 1985 and oocyte donation since 2003. The aim of this study was to investigate what motivations women and men in Sweden have to donate gametes, if they feel any ambivalence to donate, and to compare if there is any difference in motivation and ambivalence between women and men. Motivation was measured with eight statements based on previous results and clinical experience. Ambivalence was measured with a scale consisting of seven statements that addressed thoughts and feelings about the donation. The participants in the study were donors at some of the seven infertility clinics in Sweden. The dropout rate for the sperm donors was 19 %. For the egg donors the dropout rate was 17 %.. The main result showed that the main motivation for donating oocytes or semen was helping childless couples. The significant differences between women’s and men’s motivations for donating oocytes or semen were that the women were keener to helping others, while the men to a higher extent wanted to do something important, spread their genes and find out about their own fertility. The oocyte and semen donors did not feel any particular ambivalence about the decision to donate, most of them did not find it difficult to make the decision, and they would have been disappointed if they had not been allowed to donate for some reason. The conclusions to be drawn from this study are that once the donors have decided to donate, they don’t feel any particular ambivalence about the donation, and women and men have different motivations to why they are donating, even if the main motivation is the same.</p> / <p>Ofrivillig barnlöshet är ett stort problem världen över. Ett sätt att lösa problemet är att ta emot ägg eller spermier ifrån en donator. I Sverige har spermiedonation varit reglerat i lag sedan 1985 och äggdonation sedan 2003. Syftet med denna studie var att undersöka vilka motiv kvinnor och män i Sverige har till att donera ägg respektive spermier, om de känner någon ambivalens till att donera, samt att jämföra om det är någon skillnad i motiv och ambivalens mellan kvinnor och män. Motiv mättes med åtta påståenden konstruerade utifrån tidigare resultat och klinisk erfarenhet. Ambivalens mättes med en skala som bestod av sju påståenden som behandlade tankar och känslor kring donationen, Deltagarna i studien var donatorer vid någon av de sju infertilitetscentra i Sverige. Bortfallet för spermiedonatorerna var 19 %. För äggdonatorerna var bortfallet 17 %. Huvudresultatet visade att det främsta motivet hos kvinnor och män till att donera ägg respektive spermier i Sverige var att hjälpa barnlösa par. De signifikanta skillnaderna mellan kvinnors och mäns motiv till att donera ägg respektive spermier var att kvinnor var mer måna om att hjälpa andra, medan männen i högre grad ville göra något betydelsefullt, sprida sina gener och få reda på hur det stod till med den egna fertiliteteten. Ägg- och spermiedonatorerna kände ingen större ambivalens inför beslutet om att donera, de flesta tyckte inte att beslutet var svårt att ta, och de skulle ha blivit besvikna om de inte fick donera av någon anledning. Slutsatser som har dragits är att när ägg- respektive spermiedonatorer väl har bestämt sig för att donera känner de ingen större ambivalens inför donationen, och män och kvinnor har skilda motiv till varför de donerar även om huvudmotivet är detsamma.</p>

Involuntary childlessness is a big problem around the world. One way to solve the problem is to receive oocytes or semen from a donor. In Sweden, semen donation has been regulated by law since 1985 and oocyte donation since 2003. The aim of this study was to investigate what motivations women and men in Sweden have to donate gametes, if they feel any ambivalence to donate, and to compare if there is any difference in motivation and ambivalence between women and men. Motivation was measured with eight statements based on previous results and clinical experience. Ambivalence was measured with a scale consisting of seven statements that addressed thoughts and feelings about the donation. The participants in the study were donors at some of the seven infertility clinics in Sweden. The dropout rate for the sperm donors was 19 %. For the egg donors the dropout rate was 17 %.. The main result showed that the main motivation for donating oocytes or semen was helping childless couples. The significant differences between women’s and men’s motivations for donating oocytes or semen were that the women were keener to helping others, while the men to a higher extent wanted to do something important, spread their genes and find out about their own fertility. The oocyte and semen donors did not feel any particular ambivalence about the decision to donate, most of them did not find it difficult to make the decision, and they would have been disappointed if they had not been allowed to donate for some reason. The conclusions to be drawn from this study are that once the donors have decided to donate, they don’t feel any particular ambivalence about the donation, and women and men have different motivations to why they are donating, even if the main motivation is the same. / Ofrivillig barnlöshet är ett stort problem världen över. Ett sätt att lösa problemet är att ta emot ägg eller spermier ifrån en donator. I Sverige har spermiedonation varit reglerat i lag sedan 1985 och äggdonation sedan 2003. Syftet med denna studie var att undersöka vilka motiv kvinnor och män i Sverige har till att donera ägg respektive spermier, om de känner någon ambivalens till att donera, samt att jämföra om det är någon skillnad i motiv och ambivalens mellan kvinnor och män. Motiv mättes med åtta påståenden konstruerade utifrån tidigare resultat och klinisk erfarenhet. Ambivalens mättes med en skala som bestod av sju påståenden som behandlade tankar och känslor kring donationen, Deltagarna i studien var donatorer vid någon av de sju infertilitetscentra i Sverige. Bortfallet för spermiedonatorerna var 19 %. För äggdonatorerna var bortfallet 17 %. Huvudresultatet visade att det främsta motivet hos kvinnor och män till att donera ägg respektive spermier i Sverige var att hjälpa barnlösa par. De signifikanta skillnaderna mellan kvinnors och mäns motiv till att donera ägg respektive spermier var att kvinnor var mer måna om att hjälpa andra, medan männen i högre grad ville göra något betydelsefullt, sprida sina gener och få reda på hur det stod till med den egna fertiliteteten. Ägg- och spermiedonatorerna kände ingen större ambivalens inför beslutet om att donera, de flesta tyckte inte att beslutet var svårt att ta, och de skulle ha blivit besvikna om de inte fick donera av någon anledning. Slutsatser som har dragits är att när ägg- respektive spermiedonatorer väl har bestämt sig för att donera känner de ingen större ambivalens inför donationen, och män och kvinnor har skilda motiv till varför de donerar även om huvudmotivet är detsamma.

Diss. (sammanfattning) Uppsala : Univ., 2003. / Härtill 5 uppsatser.

This study examined mothers who have undergone gamete donation treatment and lack a genetic connection to their adolescent children. The study examined the mothers experience of closeness and similarity with their child, as well as their feelings regarding the child's ability to seek information and contact the donor. Experiences regarding talking to the child and others, as well as their potential desire for support were explored. The study is based on data from the longitudinal study Swedish Study of Gamete Donations (SSGD), which has collected data in five rounds since 2005. Using a mixed-methods design the current study compared egg donation mothers in heterosexual couples (n=41) and non-carrying mothers in lesbian couples (n=59). Participants responded to surveys containing rating scales and free text responses. The material was analyzed using chi2-, Mann-Whitney U-, and t-tests, as well as qualitative content analysis. The majority in both groups reported high levels of closeness to their children and more often perceived similarity in personality than appearance. Participants primarily reported positive emotions related to their child’s ability to access information about and contact the donor. There were no statistically significant differences between the groups. Some qualitative differences emerged regarding feelings about discussing the donation. A few mothers from both groups expressed a need for support. The study contributes to a broader understanding of mothers who have undergone gamete donation treatment and how interventions for these mothers can be devised. Additionally, the study confirms that these groups generally have close relationships with their children. / Studien har undersökt mammor som genomgått donationsbehandling och inte har genetisk koppling till sitt, idag tonåriga, barn. Studien undersökte mammornas upplevelse av närhet och likhet med sitt barn samt vilka känslor de har inför barnets möjlighet att söka information och ta kontakt med donatorn. Även upplevelser kring att prata med barnet och andra om donationen samt vilket eventuellt stöd mammorna önskar undersöktes. Studien bygger på data från den longitudinella studien Swedish Study of Gamete Donations (SSGD) som samlat in data i fem omgångar sedan 2005. Studien använde en mixad design för att jämföra grupperna äggdonations-mammor i heterosexuella par (n=41) och icke-bärande mammor i lesbiska par (n=59). Deltagarna har besvarat enkäter som innehöll skattningsskalor och öppna frågor. Materialet analyserades genom chi2-, Mann-Whitney U-, och t-test samt kvalitativ innehållsanalys. Majoriteten i båda grupperna upplevde hög nivå av närhet till sina barn och upplevde oftare likhet i personlighet än utseende. Deltagarna rapporterade primärt positiva känslor relaterade till barnens möjlighet till information om och kontakt med donatorn. Det fanns inga statistiskt signifikanta skillnader mellan grupperna. Dock fanns vissa kvalitativa skillnader gällande känslor och motivation till att prata om donationen. Ett fåtal mammor ur båda grupperna efterfrågade stöd. Studien bidrar till en bredare förståelse för mammor som genomgått donationsbehandling och hur insatser för dessa kan utformas samt bekräftar att dessa grupper generellt har nära relationer till sina barn.

Implantation requires complex molecular and cellular events involving coagulation, angiogenesis and immunological processes that need to be well regulated for a pregnancy to establish and progress normally.  The overall aim of this thesis was to study different models associated with atypical angiogenesis, impaired implantation and/or placentation, such as recurrent miscarriage (RM), oocyte donation (OD) and preeclampsia. Histidine-rich glycoprotein (HRG), a serum protein with angiogenic potential has been previously shown to have an impact on implantation and fertility.  In two retrospective case-control studies, women suffering from RM (Study I) and gestational hypertensive disorders (GHD) (Study IV) have been compared to healthy control women, regarding carriership of HRG genotypes (HRG A1042G and C633T SNP, respectively).  According to the findings of this thesis, heterozygous carriers of the HRG A1042G SNP suffer from RM more seldom than homozygous carriers (Study I).  Additionally, the presence of the HRG 633T allele was associated with increased odds of GHD (GHD IV).  Studies II and III comprised a national cohort of relatively young women with optimal health status conceiving singletons with donated oocytes versus autologous oocytes (spontaneously or via IVF).  We explored differences in various obstetric (Study II) and neonatal (Study III) outcomes from the Swedish Medical Birth Register.  Women conceiving with donated oocytes had a higher risk of GHD, induction of labor and cesarean section, as well as postpartum hemorrhage and retained placenta, when compared to autologously conceiving women.  OD infants had higher odds of prematurity and lower birthweight and length when born preterm, compared to neonates from autologous oocytes.  With regard to the indication of OD treatment, higher intervention but neverthelss favourable neonatal outcomes were observed in women with diminished ovarian reserve; the risk of GHD did not differ among OD recipients after adjustment. In conclusion, HRG genetic variation appears to contribute to placental dysfunction disorders.  HRG is potential biomarker that may contribute in the prediction of the individual susceptibility for RM and GHD.  Regarding OD in Sweden, the recipients-despite being of optimal age and health status- need careful preconceptional counselling and closer prenatal monitoring, mainly due to increased prevalence of hypertensive disorders and prematurity.

<p>The main aims were to investigate emotional reactions during in vitro fertilization (IVF) treatment among women and men, attitudes of IVF couples towards cryopreserved embryos and public attitudes towards various aspects of oocyte donation in Sweden. Assessments of emotional, physical and social reactions were made on a daily reaction scale and attitudes on the basis of study-specific questionnaires. Both women and men experienced the stages of oocyte retrieval and embryo transfer, as well as the luteal phase, as being particularly stressful and there was a similarity in the type of reaction pattern. Presence of supernumerary embryos for cryopreservation increased the women’s optimism, but did not seem to reduce their level of distress on the day of embryo transfer. One-third of IVF couples chose not to use their cryopreserved embryos. The main reasons among the respondents concerned family planning and too short a legally allowed time of embryo storage. There was strong support for oocyte donation among a subset of the Swedish population. Women were more positive than men towards oocyte donation and to disclosure of the origin to offspring. Factors that might increase the likelihood of women becoming oocyte donors were talking to women with experience of donating oocytes, proximity to the clinic, accessibility of counselling and having children of their own. These results indicate that different approaches to psychological care for women and men may not be warranted during IVF treatment. Contact should be maintained during the cryopreservation period in order to adress the couple’s questions and concerns about the embryos. To increase the donor pool, IVF clinics could provide information about donation to potential donors through the Internet and through experienced donors. The information to donors and recipient couples about different consequences of donation seems to be of great importance.</p>

The main aims were to investigate emotional reactions during in vitro fertilization (IVF) treatment among women and men, attitudes of IVF couples towards cryopreserved embryos and public attitudes towards various aspects of oocyte donation in Sweden. Assessments of emotional, physical and social reactions were made on a daily reaction scale and attitudes on the basis of study-specific questionnaires. Both women and men experienced the stages of oocyte retrieval and embryo transfer, as well as the luteal phase, as being particularly stressful and there was a similarity in the type of reaction pattern. Presence of supernumerary embryos for cryopreservation increased the women’s optimism, but did not seem to reduce their level of distress on the day of embryo transfer. One-third of IVF couples chose not to use their cryopreserved embryos. The main reasons among the respondents concerned family planning and too short a legally allowed time of embryo storage. There was strong support for oocyte donation among a subset of the Swedish population. Women were more positive than men towards oocyte donation and to disclosure of the origin to offspring. Factors that might increase the likelihood of women becoming oocyte donors were talking to women with experience of donating oocytes, proximity to the clinic, accessibility of counselling and having children of their own. These results indicate that different approaches to psychological care for women and men may not be warranted during IVF treatment. Contact should be maintained during the cryopreservation period in order to adress the couple’s questions and concerns about the embryos. To increase the donor pool, IVF clinics could provide information about donation to potential donors through the Internet and through experienced donors. The information to donors and recipient couples about different consequences of donation seems to be of great importance.