Who becomes a sperm donor: personality characteristics in a national sample of identifiable donors.

OBJECTIVE: To study the personality characteristics of identifiable sperm donors in a national sample in comparison with the same characteristics of a control group. DESIGN: Descriptive study. SETTING: All clinics (n=7) performing gamete donation in Sweden. POPULATION: All Swedish sperm donors recruited during 2005-08. An age-matched group of Swedish men served as controls. METHODS: Standardised questionnaires were used to measure personality. MAIN OUTCOME MEASURES: Demographics and the Temperament and Character Inventory (TCI). RESULTS: The mean age of the donors was 33.8±7.8 years (18-56 years). About one-third (36.5%) of the donors had biological children of their own. With regard to personality, significant differences were present on harm avoidance, with lower means for sperm donors (P=0.002, 95% CI -3.74 to -0.85), and on self-directedness and cooperativeness, with higher means for donors (P=0.002, 95% CI 0.97-4.19; P=0.001; 95% CI 0.75-2.95, respectively), compared with controls. This indicates that the donors in general feel less worried and suffer less from uncertainty, shyness and fatigability than controls. They also perceive themselves as being autonomous, with a capacity to take responsibility, to behave in a goal-directed manner, to be resourceful and self-acceptant, and to behave in a manner guided by meaningful values and goals. Furthermore, they describe themselves as being well integrated in humanity or society, and having a good capacity for identification with and acceptance of other people. CONCLUSIONS: The screening process at the clinics seems to generate a group of stable, mature and well-integrated donors, and this is a promising result for the future.

A randomized controlled study comparing pain experience between a newly designed needle with a thin tip and a standard needle for oocyte aspiration.

UNLABELLED: BACKGROUND; Ultrasound-guided transvaginal oocyte retrieval is often performed under local anaesthesia on an outpatient basis. The objective of this study was to compare the overall pain experience of a newly designed reduced needle (RN) compared with a thicker standard needle (SN). METHODS: A prospective, randomized, multi-centre study was performed at four different clinics from June to December 2009. The oocyte aspiration was performed under local anaesthesia, either with a needle with a reduced diameter (0.9 mm) for the last 50 mm from the tip (RN) or with a SN (1.4 mm). A total of 257 patients were randomized (RN: n = 129; SN: n = 128). The primary endpoint was the overall pain experience self-assessed and registered by the patient on a visual analogue scale (VAS 0 mm = no pain to 100 mm = unbearable pain) immediately after the oocyte retrieval. Secondary end-points such as vaginal bleeding and several embryological parameters were also registered. RESULTS: The overall pain during the oocyte retrieval procedure was significantly lower in the RN group than in the SN group (mean 21.0 mm, SD 17.5 mm and median 19.0 mm versus mean 26.0 mm, SD 19.9 mm and median 24.0 mm; P = 0.040, difference between groups mean-5.0 mm, 95% CI: 9.7 to-0.4). This was also true when adjusting for baseline characteristics such as number of follicles, number of previous oocyte pick-up, body mass index and age, by a multiple linear regression analysis. Significantly more patients (40 of 126) had less than expected vaginal bleeding in the RN group when compared with the SN group (24 of 124; 32 versus 19%; P = 0.03 and 95% CI 1.7-23.0%). No differences were found between the two needles with regard to additional i.v. analgesia, aspiration time, oocyte recovery, fertilization, cleavage rate, number of good quality embryos, number of embryos for freezing and pregnancy rate. CONCLUSIONS: Oocyte aspiration performed with the newly designed thinner-tipped needle resulted in significantly less overall pain and less vaginal bleeding, without prolonging the retrieval procedure or influence the oocyte recovery rate, when compared with a SN. Clinicaltrials.gov: NCT00924885.

Two decades after legislation on identifiable donors in Sweden: are recipient couples ready to be open about using gamete donation?

BACKGROUND Two decades after the introduction of Swedish legislation that allows children born as a result of gamete donation access to identifying information about the donor, a nationwide multicentre study on the psychosocial consequences of this legislation for recipients and donors of gametes was initiated in 2005. The aim of the present study was to investigate recipient couples' attitudes and behaviour regarding disclosure to offspring and others, attitudes towards genetic parenthood and perceptions of information regarding parenthood after donation. METHODS The present study is part of the prospective longitudinal 'Swedish study on gamete donation', including all fertility clinics performing donation treatment in Sweden. A consecutive cohort of 152 heterosexual recipient couples of donated oocytes (72% response) and 127 heterosexual recipient couples of donated sperm (81% response) accepted participation in the study. In connection with the donation treatment, male and female participants individually completed two questionnaires with study-specific instruments concerning disclosure, genetic parenthood and informational aspects. RESULTS About 90% of participants (in couples receiving anonymous donated gametes) supported disclosure and openness to the offspring concerning his/her genetic origin. Only 6% of all participants had not told other people about their donation treatment. Between 26 and 40% of participants wanted additional information/support about parenthood following donation treatment. CONCLUSIONS Two decades after the Swedish legislation of identifiable gamete donors, recipient couples of anonymously donated sperm and oocytes are relatively open about their treatment and support disclosure to offspring. Recipient couples may benefit from more information and support regarding parenthood after gamete donation. Further studies are required to follow-up on the future parents' actual disclosure behaviour directed to offspring.

Personality characteristics in a Swedish national sample of identifiable oocyte donors.

OBJECTIVE: To study the personality characteristics of identifiable oocyte donors in a national sample in comparison with normal values. DESIGN: Descriptive study. SETTING: All Swedish donation programmes. SAMPLE: In total, 181 women out of 221 donors recruited during 2005-2008. METHODS: Standardised questionnaires were used to measure personality characteristics. MAIN OUTCOME MEASURE: Demographics, temperament and character inventory (TCI). RESULTS: The majority (69%) of the donors had biological children of their own. The results from the TCI indicate that the oocyte donors were all within the normal range of character. With regard to personality, a significant difference was evident between the two groups: oocyte donors showed lower means for harm avoidance and higher scores for persistence than the controls. This indicates that the donors felt less worried, and displayed a lower level of fear of uncertainty, shyness and fatiguability, and a higher level of persistence, than the controls. In the present sample, 29 (16%) of the donors were so-called 'known donors', that is the recipient couples and the donors were known to each other. 'Known donors' displayed a mature and stable character. CONCLUSION: We found that the women who had been accepted for inclusion in this nationwide oocyte donor programme were all well adjusted and mature.

A prospective randomized trial of artificial insemination versus intercourse in cycles stimulated with human menopausal gonadotropin or clomiphene citrate.

OBJECTIVE: To determine the relative efficacy of intrauterine insemination (IUI), direct intraperitoneal insemination, and intercourse in cycles stimulated with clomiphene citrate (CC) or human menopausal gonadotropins (hMG). DESIGN: A prospective randomized trial with a 2(3) factorial design with eight different treatment alternatives. Only one cycle per couple was performed. SETTINGS: The Departments of Obstetrics and Gynecology, Central Hospital, Västerås and Akademiska Hospital, Uppsala University, Uppsala, Sweden. PATIENTS: Of 157 randomized couples with unexplained infertility including 51 cases with minimal or mild endometriosis, 148 were selected for comparison. MAIN OUTCOME MEASURE: Pregnancy rate (PR). RESULTS: Follicular stimulation with hMG gave a higher PR than with CC in the insemination cycles, 19% (10/52) and 4% (2/49), respectively, but the PRs in intercourse cycles were not significantly different for hMG and CC, 13% (3/24) and 17% (4/23), respectively. Insemination cycles and intercourse cycles had a similar overall PR, 12% (12/101) and 13% (7/47), respectively. Furthermore, IUI and direct intraperitoneal insemination did not differ in efficacy. CONCLUSION: Follicular stimulation with hMG is more effective than CC in insemination cycles, but insemination as such seems to have no beneficial effect on the PR in stimulated cycles for treatment of unexplained infertility.

Direct intraperitoneal insemination--clinical results and comparison between two methods of sperm preparation.

OBJECTIVE: To compare sperm preparation with a new self-migration method in sodium hyaluronate and a centrifugation/swim-up method and to study the efficiency of direct intraperitoneal (IP) insemination. STUDY DESIGN: Sodium hyaluronate and centrifugation/swim-up were used randomly for direct IP insemination in alternating cycles. Treatments were given with an interval of at least one untreated cycle. When ovulation occurred on weekends, the patients received only controlled ovarian hyperstimulation. SETTINGS: Department of Obstetrics and Gynecology University Hospital, Uppsala, Sweden. PATIENTS: Seventy-nine couples with unexplained infertility (n = 53), endometriosis (n = 17), and cervical factor (n = 9). INTERVENTIONS: Controlled ovarian hyperstimulation was accomplished by clomiphene citrate and gonadotropins. MAIN OUTCOME MEASURES: Sperm parameters and pregnancy rates. RESULTS: Sodium hyaluronate and centrifugation/swim-up resulted in similar conception rates, but sodium hyaluronate recovered more motile spermatozoa than centrifugation/swim-up (P less than 0.0001). The number of patients who became pregnant after direct IP insemination or controlled ovarian hyperstimulation only was significantly higher than that observed after untreated cycles (P = 0.00001 and P = 0.008, respectively). CONCLUSIONS: Sperm preparation with sodium hyaluronate can be used as an alternative to centrifugation/swim-up. Direct IP insemination appears to increase the cycle fecundity, but whether direct IP insemination/controlled ovarian hyperstimulation is more effective than controlled ovarian hyperstimulation alone has yet to be proven.

Methotrexate treatment for retained placental tissue.

Three cases of placental polyps not responding to conventional medical and surgical treatment are presented. In all three cases, hCG in serum was negative but despite this a single injection of methotrexate successfully treated the condition. It is suggested that methotrexate acts not only on dividing trophoblastic cells but also has other effects.

Reducing the number of embryos transferred in Sweden-impact on delivery and multiple birth rates.

BACKGROUND: Reduction of the number of embryos transferred has been introduced to decrease the multiple birth rates (MBRs) after IVF and the associated risks for the children. The aim of this report is to present the effect of two steps in reduction of the number of embryos transferred, when applied in the majority of the patients, on national data for delivery and MBR after IVF in Sweden. METHODS: This observational study is based on annual reports from all IVF clinics in Sweden to the National Board of Health and Welfare for the time period 1991-2004. RESULTS: The main finding is that despite a successive reduction in the number of embryos transferred, delivery rates were maintained at around 26% while MBR decreased dramatically, from about 35% to around 5%. The same pattern was noticed, independent of age, for all women below 40. In comparison with the USA, lower delivery and MBR were noted for Sweden whereas a higher 'birth per embryo transferred' was found. CONCLUSIONS: Single embryo transfer (SET) results in satisfactory delivery rates and a dramatic decrease in the MBRs, also when applied on a broad scale. The experience from Sweden ought to encourage other countries to introduce SET more widely.

Fertility awareness, intentions concerning childbearing, and attitudes towards parenthood among female and male academics.

BACKGROUND: Postponing childbirth is becoming increasingly common in Western countries, especially among groups with higher education qualifications. It is relatively unknown to what extent women and men are aware of the age-related decline in female fertility. The aim was to investigate university students' intentions and attitudes to future parenthood and their awareness regarding female fertility. METHODS: Postal survey of a randomly selected sample of 222 female (74% response) and 179 male (60% response) university students. RESULTS: Female and male university students in Sweden have largely positive attitudes towards parenthood and want to have children. Women, in comparison to men, were significantly more concerned about problems related to combining work and children. Both women and men had overly optimistic perceptions of women's chances of becoming pregnant. About half of women intended to have children after age 35 years and were not sufficiently aware of the age-related decline of female fecundity in the late 30s. CONCLUSIONS: University students plan to have children at ages when female fertility is decreased without being sufficiently aware of the age-related decline in fertility. This increases the risk of involuntary infertility in this group, which is alarming in view of the great importance they put on parenthood.

Hormone and ultrasound parameters in ovarian stimulation cycles for direct intraperitoneal insemination.

To determine hormonal and ultrasound parameters associated with pregnancies, 115 women with unexplained infertility (n = 82), endometriosis (n = 22) or cervical factor (n = 11) were treated with direct intraperitoneal insemination (DIPI) after ovarian stimulation with clomiphene citrate and human menopausal gonadotrophins (HMG). Twenty women conceived and were compared with the remaining 95 non-pregnant women during one treatment cycle. Women with basal FSH levels less than or equal to 1.25 micrograms/l responded with higher oestradiol levels (P less than 0.0001), with the development of more follicles (P less than 0.05) and higher progesterone levels (P less than 0.05) than women with basal FSH levels greater than 1.25 micrograms/l, but the conception rates were similar. Women with miscarriages or biochemical pregnancies had a higher basal FSH value than both the women with term pregnancies and the non-pregnant women. Women with at least 3 preovulatory follicles greater than or equal to 15 mm had a higher pregnancy rate than those with fewer follicles, but a further increase was not observed above that number. The endometrium was thicker on the day of ovulation induction in cycles leading to a term pregnancy than in cycles without conception or with a biochemical pregnancy. No term pregnancy was observed when the endometrium was thinner than 8 mm. Women with a short luteal phase (less than 12 days) had a higher ratio of oestradiol/progesterone in the midluteal phase than women with a luteal phase of greater than or equal to 12 days and pregnant women.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of the ability of two sperm preparation techniques to remove microbes.

The ability of a new sperm preparation method--self migration in sodium hyaluronate (SH)--to remove microbes from samples was compared to that of the traditional method of centrifugation/swim up (CS). Two 1-ml aliquots were taken from 20 semen samples used for inseminations, and prepared by each of the methods. Samples for culture were taken immediately before wash and at 2 and 24 h after. Microbes were found in all raw semen samples with a mean concentration of 47.8 x 10(3) colony forming units per ml (c.f.u./ml). After preparation and 2 h incubation with and without penicillin, both CS and SH were found greatly to reduce the number of isolates. There were no differences between the ability of the two methods to reduce microbe concentration, although SH recovered more progressive motile spermatozoa than CS (P less than 0.05). When penicillin preparation was omitted, both the CS and SH methods resulted in significantly more isolates after 24 h of incubation. This effect of penicillin preparation was also evident after only 2 h of incubation with CS, but not with SH. No clinical signs of infection were observed among women receiving treatment. We conclude that sperm preparation by self migration in sodium hyaluronate is a simple and safe method to remove microbes and to recover motile spermatozoa.

Intrauterine insemination and comparison of two methods of sperm preparation.

In a study of intrauterine inseminations (IUI) after clomiphene stimulation, a randomized comparison was made between a new method of sperm preparation, self migration in sodium hyaluronate (SH), and a traditional method, centrifugation and swim up (CS). After two IUI cycles with either SH or CS, the sperm preparation method was swapped and the patients received another two IUI cycles. Interjacent cycles of natural intercourse after clomiphene treatment served as the control. The SH method resulted in a significantly higher percentage recovery of progressive motile spermatozoa than the CS method, 17.7% versus 8.6% (P less than 0.01). The sperm samples were prepared by SH in 68 cycles and by CS in 57 cycles, resulting in six and five pregnancies, respectively. Pregnancies were obtained in 11 of 125 IUI cycles (8.8%) and in 3 of 124 control cycles (2.4%) (P less than 0.05). The pregnancy rate following IUI was highest in the patients with cervical factor (35%) and asthenozoospermia (23%), while none became pregnant in the group with oligozoospermia. In the unexplained infertility group, no difference between the pregnancy rates in IUI cycles and control cycles was seen. SH is a simple and rapid method of sperm preparation and it appears to give a high recovery of motile spermatozoa and a number of pregnancies which is comparable to that of CS. Treatment with IUI in cycles with a simple stimulation protocol seems to be valuable in cases involving either a cervical factor or asthenozoospermia.

Addition of gonadotrophin-releasing hormone agonist and/or two inseminations with husband's sperm do not improve the pregnancy rate in superovulated cycles.

BACKGROUND: A prospective randomized study was performed to evaluate the addition of a gonadotropin releasing hormone agonist (GnRH-a) during treatment with human menopausal gonadotropins (hMG) in cycles with artificial inseminations with husband's washed sperm (AIH). We also compared the pregnancy rate per cycle after one versus two AIHs. METHODS: We designed a 22 factorial trial. A total of 172 couples with unexplained infertility (n=88), endometriosis (n=39), or cervical (n=24) or male (n=21) factors were included, of whom 161 fulfilled the inclusion criteria and treatment. Eighty-one women were treated with GnRH-a/hMG and another 80 with hMG only, respectively. RESULTS: The pregnancy rates did not differ between the two stimulation protocols (12% for GnRH-a/hMG and 9% for hMG). With GnRH-a/hMG more follicles >15 mm (3.4 and 2.4, respectively; p<0.01) and a higher multiple pregnancy rate after 20 weeks of gestation were observed (55% vs. 0%; p<0.05). Eighty-seven women were treated with one AIH, whereas 65 women received two AIHs on two consecutive days. The pregnancy rates were similar in these two groups (11% and 9% respectively; n.s.) CONCLUSION: It is concluded that neither addition of GnRH-a before and during controlled ovarian hyperstimulation nor two AIHs compared with one single AIH per cycle has a beneficial effect on the pregnancy rate. However, GnRH-a increases the risk for multiple pregnancies.

Prognostic factors for the success rate of embryo freezing.

To find some prognostic factors for the outcome of frozen-thawed cycles, we have retrospectively analysed all frozen pre-embryos that were thawed during 1993 and 1994 at two in-vitro fertilization (IVF) units in Sweden. Supernumerary pre-embryos were frozen from 551 oocyte retrievals and these resulted in 660 frozen-thawed cycles which lead to 623 thawed embryo transfers. The outcome of these transfers was 137 clinical pregnancies with a pregnancy rate of 22% per frozen-thawed embryo transfers. Women <40 years of age had a higher birth rate than those > or =40 years, 19 and 5% respectively (P < 0.01). Transfers with two and three pre-embryos resulted in pregnancy rates of 23 and 27%, respectively, compared with 14% for transfer of one embryo. A pregnancy resulting from the initial embryo transfers had a predictive value for results of the subsequent frozen-thawed cycle. Embryo grade and cleavage stage at the time of freezing was important for the survival of the frozen-thawed pre-embryos. The pregnancy rate was not influenced by the cleavage stage, but a tendency toward a lower pregnancy rate was seen for the embryos with lower grading. To conclude, cryopreservation seems to be beneficial in women <40 years of age, who have supernumerary pre-embryos of good quality for freezing and of which at least two can be transferred.

Avoiding multiple pregnancies in ART: consideration of new strategies.

To maximize pregnancy rates, physicians who perform IVF, often transfer multiple embryos, which increases the multiple birth risk. Multiple birth infants are at significant risk for a number of adverse outcomes including preterm delivery, low birth weight, congenital malformations, fetal and infant deaths and long term morbidity and disability among survivors. Since the ultimate goal for an IVF treatment is the birth of a healthy infant, an important issue for all kinds of assisted reproductive technologies (ART) must be the reduction or elimination of multiple pregnancies. In this article, different strategies to avoid multiple births in ART are discussed.

A3--a novel colon and pancreatic cancer reactive antibody from a primate phage library selected using intact tumour cells.

The identification of novel tumour-associated antigens (TAAs) is pivotal for progression in the fields of tumour immunotherapy and diagnosis. In the present study, we have developed, based on flow cytometric evaluation and use of a mini-library composed of specific antibody clones linked to different antibiotic resistance markers, methods for positive and subtractive selection of phage antibodies employing intact cells as the antigen source. An scFv phage library (2.7 x 10(7)) was constructed from a primate (Macaca fascicularis) immunised with pooled human colon carcinomas. This library was selected for 3 rounds by binding to Colo 205 colon adenocarcinoma cells and proteolytic elution followed by phage amplification. Several antibodies reactive with colon carcinomas and with restricted reactivity to a few epithelial normal tissues were identified by immunohistochemistry. One clone, A3 scFv, recognised an epitope that was homogeneously expressed in 11/11 of colon and 4/4 pancreatic carcinomas studied and in normal tissue restricted to subtypes of epithelia in the gastrointestinal tract. The A3 scFv had an apparent overall affinity approximately 100-fold higher than an A3 Fab, suggesting binding of scFv homodimers. The cell surface density of the A3 epitope, calculated on the basis of Fab binding, was exceptionally high, approaching 3 million per cell. We also demonstrate efficient T-cell-mediated killing of colon cancer cells coated with A3 scFv fused to the low MHC class II binding superantigen mutant SEA(D227A). The identified A3 molecule thus represents a TAA with properties that suggest its use for immunotherapy of colon and pancreatic cancer.

Phage-selected primate antibodies fused to superantigens for immunotherapy of malignant melanoma.

The high-molecular-weight melanoma-associated antigen, HMW-MAA, has been demonstrated to be of potential interest for diagnosis and treatment of malignant melanoma. Murine monoclonal antibodies (mAb) generated in response to different epitopes of this cell-surface molecule efficiently localise to metastatic lesions in patients with disseminated disease. In this work, phage-display-driven selection for melanoma-reactive antibodies generated HMW-MAA specificities capable of targeting bacterial superantigens (SAg) and cytotoxic T cells to melanoma cells. Cynomolgus monkeys were immunised with a crude suspension of metastatic melanoma. A strong serological response towards HMW-MAA demonstrated its role as an immunodominant molecule in the primate. Several clones producing monoclonal scFv antibody fragments that react with HMW-MAA were identified using melanoma cells and tissue sections for phage selection of a recombinant antibody phage library generated from lymph node mRNA. One of these scFv fragments, K305, was transferred and expressed as a Fab-SAg fusion protein and evaluated as the tumour-targeting moiety for superantigen-based immunotherapy. It binds with high affinity to a unique human-specific epitope on the HMW-MAA, and demonstrates more restricted cross-reactivity with normal smooth-muscle cells than previously described murine mAb. The K305 Fab was fused to the superantigen staphylococcal enterotoxin A (D227A) [SEA(D227A)], which had been mutated to reduce its intrinsic MHC class II binding affinity, and the fusion protein was used to demonstrate redirection of T cell cytotoxicity to melanoma cells in vitro. In mice with severe combined immunodeficiency, carrying human melanoma tumours, engraftment of human lymphoid cells followed by treatment with the K305Fab-SEA(D227A) fusion protein, induced HMW-MAA-specific tumour growth reduction. The phage-selected K305 antibody demonstrated high-affinity binding and selectivity, supporting its use for tumour therapy in conjunction with T-cell-activating superantigens.