A multi-centre phase 3 study comparing efficacy and safety of Bemfola(®) versus Gonal-f(®) in women undergoing ovarian stimulation for IVF.

Bemfola (follitropin alfa) (Finox AG, Switzerland), a new recombinant FSH, has a comparable pharmacological profile to that of Gonal-f (Merck Serono, Germany), the current standard for ovarian stimulation. A randomized, multi-centre, Phase 3 study in women undergoing IVF or intracytoplasmic sperm injection (n = 372) showed Bemfola yielding similar efficacy and safety profiles to Gonal-f. Women aged 20-38 years of age were randomized 2:1 to receive a single, daily, subcutaneous 150 IU dose of either Bemfola or Gonal-f. This study tested equivalence in the number of retrieved oocytes using a pre-determined clinical equivalence margin of ±2.9 oocytes. Compared with Gonal-f, Bemfola treatment resulted in a statistically equivalent number of retrieved oocytes (Bemfola 10.8 ± 5.11 versus Gonal-f 10.6 ± 6.06, mean difference: 0.27 oocytes, 95% confidence interval: -1.34, 1.32) as well as a similar clinical pregnancy rate per embryo transfer in first and second cycles (Bemfola: 40.2% and 38.5%, respectively; Gonal-f: 48.2% and 27.8%, respectively). No difference in severe ovarian hyperstimulation syndrome was observed between treatment groups (Bemfola: 0.8%; Gonal-f: 0.8%). This study demonstrates similar clinical efficacy and safety profiles between Bemfola and Gonal-f, and suggests that Bemfola can be an appropriate alternative in ovarian stimulation protocols.

A 10-year follow up of reproductive function in women treated for childhood cancer.

Previously, this study group found that female childhood cancer survivors could be at risk of early cessation of fertility. The aim of the present study was to evaluate reproductive function in the same group of survivors 10 years after the initial study. Of the original cohort of 100, 71 were re-examined. Thirty-six survivors reported regular menstrual cycles. When they were compared with 210 controls, they differed significantly in antral follicle count (AFC) (median 15 versus 18, P=0.047) but not in anti-Müllerian hormone (AMH) (median 13.0 versus 17.8 pmol/l). Survivors cured with minimal gonadotoxic treatment had significantly higher AMH and AFC compared with survivors cured with either potentially gonadotoxic treatment or treatment including alkylating chemotherapy and ovarian irradiation (20.0, 5.8 and <3 pmol/l, P<0.001; and 15, 9 and 2, P=0.03, respectively). Thirty-eight survivors had achieved at least one live birth. Complicated second-trimester abortions (n=4) were observed primarily in survivors cured with radiotherapy affecting pelvic organs. In conclusion, childhood cancer survivors have signs of diminished ovarian reserve. However, if the ovarian function is preserved in the early to mid-twenties, it is likely to persist until the mid-thirties, giving a good chance of childbearing.

Expression of the vitamin D metabolizing enzyme CYP24A1 at the annulus of human spermatozoa may serve as a novel marker of semen quality.

Vitamin D (VD) is important for male reproduction in mammals and the VD receptor (VDR) and VD-metabolizing enzymes are expressed in human spermatozoa. The VD-inactivating enzyme CYP24A1 titrates the cellular responsiveness to VD, is transcriptionally regulated by VD, and has a distinct expression at the sperm annulus. Here, we investigated if CYP24A1 expression serves as a marker for VD metabolism in spermatozoa, and whether CYP24A1 expression was associated with semen quality. We included 130 men (53 healthy young volunteers and 77 subfertile men) for semen analysis and immunocytochemical (ICC) detection of CYP24A1. Another 40 men (22 young, 18 subfertile) were tested for in vitro effects of 1,25(OH)(2)D(3) on intracellular calcium concentration ([Ca(2+)](i)) and sperm motility. Double ICC staining showed that CYP24A1 and VDR were either concomitantly expressed or absent in 80% of the spermatozoa from young men. The median number of CYP24A1-expressing spermatozoa was 1% in subfertile men and thus significantly (p < 0.0005) lower than 25% in spermatozoa from young men. Moreover, CYP24A1 expression correlated positively with total sperm count, -concentration, -motility and -morphology (all p < 0.004), and the percentage of CYP24A1-positive spermatozoa increased (15 vs. 41%, p < 0.0005) after percoll-gradient-centrifugation. We noticed that the presence of >3% CYP24A1-positive spermatozoa distinguished young men from subfertile men with a sensitivity of 66.0%, a specificity of 77.9% and a positive predictive value of 98.3%. Functional studies revealed that 1,25(OH)(2)D(3) increased [Ca(2+)](i) and sperm motility in young healthy men, while 1,25(OH)(2)D(3) was unable to increase motility in subfertile patients. In conclusion, we suggest that CYP24A1 expression at the annulus may serve as a novel marker of semen quality and an objective proxy for sperm function.

Risk of ovarian failure and fertility preserving methods in girls and adolescents with a malignant disease.

Girls and young women suffering from a malignant disease that requires treatment with chemo- and/or radiotherapy are at risk of losing fertility. The most significant risk factors are age and type of treatment given. Preserving fertility is of high priority to both the young patient and her parents. This article reviews the effect of chemo- and radiotherapy on gonadal function, and thus fertility, and offers different fertility preserving methods based on the literature. Cryopreservation of ovarian tissue is a possible way of preserving fertility in this group of patients in the future.

Savanna fires increase rates and distances of seed dispersal by ants.

Myrmecochory (seed dispersal by ants) is a prominent dispersal mechanism in many environments, and can play a key role in local vegetation dynamics. Here we investigate its interaction with another key process in vegetation dynamics-fire. We examine ant dispersal of seeds immediately before and after experimental burning in an Australian tropical savanna, one of the world's most fire-prone ecosystems. Specifically, our study addressed the effects of burning on: (1) the composition of ants removing seeds, (2) number of seed removals, and (3) distance of seed dispersal. Fire led to higher rates of seed removal post-fire when compared with unburnt habitat, and markedly altered dispersal distance, with mean dispersal distance increasing more than twofold (from 1.6 to 3.8 m), and many distance dispersal events greater than the pre-fire maximum (7.55 m) being recorded. These changes were due primarily to longer foraging ranges of species of Iridomyrmex, most likely in response to the simplification of their foraging landscape. The significance of enhanced seed-removal rates and distance dispersal for seedling establishment is unclear because the benefits to plants in having their seeds dispersed by ants in northern Australia are poorly known. However, an enhanced removal rate would enhance any benefit of reduced predation by rodents. Similarly, the broader range of dispersal distances would appear to benefit plants in terms of reduced parent-offspring conflict and sibling competition, and the location of favourable seedling microsites. Given the high frequency of fire in Australian tropical savannas, enhanced benefits of seed dispersal by ants would apply for much of the year.

Endocrine profile in serum and follicular fluid differs after ovarian stimulation with HP-hMG or recombinant FSH in IVF patients.

BACKGROUND: Highly purified menotrophin (HP-hMG) has been associated with fewer oocytes retrieved and a higher proportion of top-quality embryos compared with recombinant FSH (rFSH). METHODS: A randomized, assessor-blind, multinational trial in 731 women undergoing IVF after stimulation with HP-hMG (MENOPUR) (n = 363) or rFSH (GONAL-F) (n = 368) following a long GnRH agonist protocol was conducted. Blood was collected before, during and after stimulation. Fluid was collected from follicles > or =17 mm. RESULTS: Serum androstenedione, total testosterone and free androgen index (FAI) were higher (P < 0.001) with HP-hMG than with rFSH after starting stimulation. At the end of stimulation, serum estradiol was higher (P = 0.031) with HP-hMG, whereas progesterone was higher (P < 0.001) with rFSH, even after adjusting for ovarian response. Serum LH was not different between treatments. Mean mid- and end-follicular hCG levels in the HP-hMG group were 2.5 and 2.9 IU/l, respectively. Follicular fluid levels of FSH, LH, hCG, androstenedione, testosterone, FAI and estradiol and ratios of estradiol:androstenedione, estradiol:total testosterone and estradiol:progesterone were higher (P < 0.001) with HP-hMG, whereas progesterone was higher (P < 0.001) with rFSH. CONCLUSION: Major differences in serum and follicular fluid endocrine profile exist after stimulation with HP-hMG or rFSH. Exogenous LH activity induces a differential endocrine environment influencing oocyte quantity and quality, which may be of relevance for clinical outcome.

The influence of body weight on response to ovulation induction with gonadotrophins in 335 women with World Health Organization group II anovulatory infertility.

OBJECTIVE: To assess the influence of body weight on the outcome of ovulation induction in women with World Health Organization (WHO) group II anovulatory infertility. DESIGN: The combined results of two studies in which either a highly purified urinary follicle-stimulating hormone or highly purified urinary menotrophin were compared with recombinant follicle-stimulating hormone. SETTING: Thirty-six fertility clinics. POPULATION: A total of 335 women with WHO group II anovulatory infertility failing to ovulate or conceive on clomifene citrate. METHODS: Ovarian stimulation using a low-dose step-up protocol. MAIN OUTCOME MEASURES: The effects of body weight on ovarian response, ovulation rate and pregnancy rate after one treatment cycle. RESULTS: With increasing body mass index (BMI), a higher threshold dose of gonadotrophins was required and there were more days of stimulation; yet, despite a greater concentration of antral follicles, there were fewer intermediate and large follicles. There was no difference in the rates of ovulation and clinical pregnancy in relation to body weight. CONCLUSIONS: Body weight affects gonadotrophin requirements but not overall outcome of ovulation induction in women with anovulatory polycystic ovary syndrome and a BMI of less than 35 kg/m2.

Androgen priming using aromatase inhibitor and hCG during early-follicular-phase GnRH antagonist down-regulation in modified antagonist protocols.

BACKGROUND: Temporary exposure of follicles to increased levels of androgens may enhance their sensitivity to FSH. The aim of this study was to increase the intraovarian androgen level using aromatase inhibitors and hCG before controlled ovarian stimulation (COH) and to test this concept clinically. METHODS: In a prospective, non-randomized study, 45 patients were treated in modified antagonist protocols including early-follicular-phase down-regulation and androgen priming before COH. All patients received cetrorelix, 3 mg s.c., on cycle days 2 and 5. Group I (n=15) received no other pretreatment. Group II (n=15) received 1 daily tablet of aromatase inhibitor, letrozole 2.5 mg, from cycle days 2 to 8. Group III (n=15) received letrozole as Group II and 1250 IU of hCG s.c. on cycle day 2. From cycle day 8, all patients were stimulated with highly purified menotrophin in a flexible antagonist protocol. RESULTS: Aromatase inhibitor increased the level of testosterone in follicular fluid (P<0.002), but not in plasma. Androgen priming with aromatase inhibitor and hCG increased the number of good-quality embryos (P=0.015) but did not increase the implantation rate. CONCLUSIONS: The use of aromatase inhibitor before COH significantly influences the local endocrine environment before and during stimulation. Androgen priming with both aromatase inhibitor and hCG may result in more good-quality embryos.

Spontaneous abortion in IVF couples--a role of male welding exposure.

BACKGROUND: Fume from welding of stainless steel contains hexavalent chromium, which in animal studies can induce paternally mediated spontaneous abortion. Human studies have shown conflicting results. The best studies include early pregnancy experience, but these are expensive to conduct. In vitro fertilization (IVF) provides new design opportunities. Our aim was to study pregnancy survival in IVF treated women with respect to paternal welding exposure. METHODS: We mailed a questionnaire to 5879 couples from the Danish IVF register that covers all IVF treatments after 1993 (response ratio 68.2%). A subgroup of male metal workers received a second questionnaire on exposure to welding (n = 319 men, response ratio 77%). Information on outcome was collected from national health registers. Survival of the first hCG-positive pregnancy was analysed using Cox regression. RESULTS: The proportion of pregnancies terminated by spontaneous abortion before 28 gestational weeks was 18% (n = 91 pregnancies) and 25% (n = 128) in pregnancies with paternal exposure to stainless steel welding and mild steel welding, respectively. In the reference group of 2925 pregnancies the abortion ratio was 28%. The risk ratio for pregnancies with paternal exposure to stainless steel was 0.6 (95% CI 0.4-1.0). CONCLUSIONS: We found no increased risk of spontaneous abortion in IVF treated women, who became pregnant by a man exposed to welding of any sort. Since the process of fertilization and selection of IVF pregnancies differs from natural pregnancies the negative results need not apply to other pregnancies.

Pesticide exposure in male farmers and survival of in vitro fertilized pregnancies.

BACKGROUND: Male-mediated spontaneous abortion is well described among animals, but less well documented in humans. Studies that include early pregnancy experience are expensive to conduct, but IVF provides new opportunities. MATERIALS AND METHODS: The Danish IVF register covers all IVF treatments performed after 1993. We mailed a questionnaire to 5879 women (response rate 68.2%). A subgroup of exposed male partners received a questionnaire on specific exposure to pesticides and growth retardants (n = 128 men, response rate 81.3%). Information on outcome was collected from national health registers. Survival of the first HCG-positive pregnancy was analysed using Cox regression. RESULTS: The proportion of pregnancies terminated by spontaneous abortion before 28 gestational weeks was 19.7% (n = 66 pregnancies), 19.7% (n = 61), 21.3% (n = 47) and 22.2% (n = 18) in pregnancies with paternal exposure to herbicides, fungicides, pesticides and growth retardants. respectively. In the reference group of 2925 pregnancies, the abortion rate was 28.4%. The differences in survival were not statistically significant. CONCLUSIONS: We found no increased risk of spontaneous abortion in IVF-treated women attributable to paternal agricultural application of pesticides and growth retardants. Exposure to potentially harmful pesticides in Denmark is relatively low, and the findings are restricted to countries with similar standards of protection.

Time to pregnancy and semen parameters: a cross-sectional study among fertile couples from four European cities.

BACKGROUND: In fertile populations, little is known about the association between semen parameters and time to pregnancy (TTP). METHODS: Pregnant women from Copenhagen, Edinburgh, Paris and Turku who conceived without medical intervention were asked for their TTP (942 couples), and their partners provided a semen sample. The proportion of morphologically normal sperm and the multiple anomalies index (MAI, ratio of the total number of anomalies to the number of abnormal sperm) were centrally estimated. We estimated rate ratios for the occurrence of a pregnancy by a discrete survival model, adjusted for sexual activity and female factors affecting fecundity. RESULTS: Increasing sperm concentration influenced TTP up to 55 x 10(6)/ml. The proportion of morphologically normal sperm influenced TTP up to 39% according to David's criteria, and this association held among the subjects with a sperm concentration >55 x 10(6)/ml. For strict criteria, the threshold value was 19% normal sperm. An increase of 0.5 in MAI was associated with an adjusted rate ratio for the occurrence of a pregnancy of 0.68 (95% confidence interval: 0.54-0.85). CONCLUSIONS: These results highlight the importance of sperm morphology parameters and indicate that the effect of proportion of normal sperm on TTP may be independent of sperm concentration.

Assisted reproductive technology in Europe, 1998. Results generated from European registers by ESHRE. European Society of Human Reproduction and Embryology.

European results of assisted reproductive techniques from treatments initiated during 1998 are presented in this second ESHRE report. Data was collected from 18 European countries usually from pre-existing national registers. A total of 521 clinics from these 18 countries reported 232 443 cycles: IVF 103 919 intracytoplasmic sperm injection (ICSI) 89 192 unclassified fertilization method 667 frozen embryo replacement (FER) 34 03 oocyte donations (OD) 4629. In nine countries where all clinics reported to the register a total of 128 801 cycles were performed in a population of 165 million corresponding to 781 cycles per million inhabitants 3.2 cycles per 1000 women aged 15-49 years. After IVF ICSI the distribution of transfer of 1, 2, 3 > or =4 embryos was 11.5, 37.2, 42.0 and 9.4% respectively. Huge differences existed between countries. For IVF the clinical pregnancy rate per aspiration per transfer was 23.2% 27.0% respectively. For ICSI the corresponding rates were 24.8% 26.8%. The distribution of singleton, twin, triplet, quadruplet deliveries for IVF and ICSI combined was 73.7, 23.9, 2.3 and 0.1%. This gives a total multiple delivery rate of 26.3%. The range of triplet deliveries after IVF and ICSI differed from 0.2-5.3% between countries. Compared with 1997, the number of reported cycles has increased by 14% and the number of reporting clinics by 8%. The clinical pregnancy rate per transfer increased from 26.1 to 27.0% after IVF and from 26.4 to 26.8% after ICSI. Multiple deliveries after IVF and ICSI decreased from 29.6 to 26.3%.

[Cryopreservation of human ovarian tissue. Method of freezing and therapeutic use]. / Kryopraeservering af humant ovarievaev. Metoder til nedfrysning og terapeutisk anvendelse.

The medical treatment of various cancers may, as long-term sequelae, cause infertility in girls and young women. In order to preserve the fertility of such women, techniques to cryopreserve ovarian tissue have gained considerable interest during recent years. The ovarian tissue is cryopreserved before cancer treatment is commenced, and first replaced when the woman has been cured. Based on the successful results from the use of this technique in test animals, where normal live young have been born, cryopreservation of human ovarian tissue has been initiated in a number of fertility clinics worldwide over the last few years. So far, only two women have experienced transplantation of cryopreserved ovarian tissue. Menstrual cycles and oestradiol production were restored in both women, but restoration of fertility have not yet been demonstrated. This review describes the technique and its present possibilities and limitations. The legal aspects in Denmark are presented and some ethical aspects described.

Regional differences in semen quality in Europe.

Recent reports have indicated a decrease in semen quality of men in some countries, and suggested regional differences. A study was undertaken of semen samples from 1082 fertile men from four European cities (Copenhagen, Denmark; Paris, France; Edinburgh, Scotland; and Turku, Finland). Semen analysis was standardized, inter-laboratory differences in assessment of sperm concentration were evaluated, and morphology assessment centralized. Lowest sperm concentrations and total counts were detected for Danish men, followed by French and Scottish men. Finnish men had the highest sperm counts. Men from Edinburgh had the highest proportion of motile spermatozoa, followed by men from Turku, Copenhagen and Paris. Only the differences between Paris/Edinburgh and Paris/Turku were statistically significant (P < 0.003 and P < 0.002 respectively). No significant differences in morphology were detected. A general seasonal variation in sperm concentration (summer 70% of winter) and total sperm count (summer 72% of winter) was detected. Semen quality of a 'standardized' man (30 years old, fertile, ejaculation abstinence of 96 h) were estimated. Typically, sperm concentrations (x 10(6)/ml) for winter/summer were: Turku 132/93; Edinburgh 119/84; Paris 103/73; and Copenhagen 98/69. These differences in semen quality may indicate different environmental exposures or lifestyle changes in the four populations. However, it remains to be seen whether such changes can account for these differences. These data may also serve as a reference point for future studies on time trends in semen quality in Europe.

Single intragenic microsatellite preimplantation genetic diagnosis for cystic fibrosis provides positive allele identification of all CFTR genotypes for informative couples.

This study is part of a strategy aimed at using fluorescent polymerase chain reaction (PCR) on informative genetic microsatellite markers as a diagnostic tool in preimplantation genetic diagnosis (PGD) of severe monogenic disease. Two couples, both of whom had previously had children who were compound heterozygote for severe cystic fibrosis mutations, were offered PGD using fluorescent PCR of the highly polymorphic cystic fibrosis transmembrane conductance regulator (CFTR) intragenic microsatellite marker IVS17bTA. Cleavage-stage embryo biopsy followed by PCR resulted in transfer of one unaffected carrier embryo for each couple. This approach eliminates the need for single cell multiplex PCR strategies to detect CF compound heterozygotes. It also provides a control of chromosome 7 ploidy in the blastomeres and a selection against allele dropout by positive detection of each CFTR copy of all genotypes in preimplantation embryos from genetically informative families.

Embryo quality and developmental potential is compromised by age.

AIMS: The aim of this retrospective study was to assess whether and how the age of the woman affects the quality and developmental potential of the oocytes and embryos in an ART program. METHOD AND MATERIAL: A total of 878 IVF cycles was included as a consecutive series of single transfers (n=292), dual transfers (n=366) and triple transfers (n=220), where all the transferred embryos in each cycle were of identical quality score and identical cleavage stage. RESULTS: We found a highly significant decrease in oocyte recovery with increasing age with about one oocyte per 2.3 years (95% CI 1.8 years to 3.1 years, p<0.0001). Further, we found that the number of oocytes that cleaved declined significantly with increasing age with one per 3.7 years (95% CI 2.7 years to 5.5 years, p<0.0001). This decline was mainly due to the decline in number of oocytes retrieved as the ratio of aspirated oocytes that cleaved with increasing age (approx. -0.04/10 year 95% CI: -0.10; +0.009) was not significantly different (p=0.10). The percentage of transfers using fragmented embryos did not increase significantly with increasing age (p=0.08). The odds of fragmentation increased by 3% per year. The average number of embryos transferred decreased significantly (p=0.03) with age from approximately 2.1 at the age of 25 to approximately 1.8 at the age of 40. In a selected subgroup of embryos all consisting of good quality embryos, a significant decrease was found in implantation rate with increasing age (approx. -0.08/10 years, 95% CI: -1.6; +0.00, p=0.05). Of the 357 pregnancies achieved in this study we found a significantly decreased ongoing pregnancy rate and a significantly increased abortion rate with increasing age (p=0.03). The decrease in the rate of ongoing pregnancies was almost linear, decreasing by approximately 1.5% per year. CONCLUSIONS: We conclude that age has an impact throughout a woman's reproductive life and that it is important to realize that the age-related decline in fertility may start already in the late twenties and not in the mid-thirties as is generally assumed.

Assisted reproductive technology in Europe, 1997. Results generated from European registers by ESHRE. European IVF-Monitoring Programme (EIM), for the European Society of Human Reproduction and Embryology (ESHRE).

European results of assisted reproductive techniques from treatments initiated during 1997 are presented in this first ESHRE report. Data were collected from 18 European countries, usually from already-existing national registers. A total of 482 clinics from these 18 countries reported 203 893 cycles. In 10 countries with complete registration, 133215 cycles were performed in a population of 174 million, corresponding to 765 cycles per million inhabitants. After IVF and intracytoplasmic sperm injection (ICSI), the distribution of transfer of one, two, three and four or more embryos was 11.5, 35.9, 38.4 and 14.3% respectively. Huge differences existed between countries. For IVF, the clinical pregnancy rate per transfer was 26.1%, and the delivery rate per embryo transfer 20.9%. For ICSI, the corresponding rates were 26.4% and 21.5%. Singleton, twin, triplet and quadruplet delivery rates for IVF were 70.4, 25.8, 3.6 and 0.2% respectively, giving a total multiple delivery rate for IVF of 29.6%. After ICSI, the corresponding rates were 71.7, 25.2, 2.9 and 0.1%, amounting to a total multiple delivery rate of 28.2%. The range of triplet delivery rates after IVF range from 0.4% to 11.9% among countries.

Progesterone supplementation during early gestation after in vitro fertilization has no effect on the delivery rate.

OBJECTIVE: To compare the delivery rate with IVF or ICSI in women who did and did not receive progesterone supplementation in the first 3 weeks after a positive hCG test result. DESIGN: Retrospective study. SETTING: Fertility Clinic, Rigshospitalet University Hospital, Copenhagen, Denmark. PATIENT(S): 200 pregnant women who did not receive progesterone (intervention group) and 200 pregnant women who received progesterone for 3 weeks after a positive hCG result. INTERVENTION(S): In the study group, vaginal progesterone therapy was withdrawn on the day of positive hCG result. In the control group, treatment with progesterone, 600 mg/d, was continued for 3 weeks after a positive hCG result. Both groups received 600 mg of progesterone starting on the day of embryo replacement until testing positive for pregnancy 14 days after embryo transfer. MAIN OUTCOME MEASURES: Delivery rate. RESULT(S): The number of deliveries was 126 in the study group and 128 in the control group. CONCLUSION(S): The delivery rate was the same in pregnant women who received and those who did not receive progesterone for 3 weeks after a positive hCG result. Progesterone supplementation for more than 2 weeks after embryo transfer may therefore yield no benefit in terms of pregnancy.

Danish National IVF Registry 1994 and 1995. Treatment, pregnancy outcome and complications during pregnancy.

SUBJECT: Data from the compulsory Danish National IVF Registry from 1994 and 1995 regarding treatments, abortions and complications following assisted reproductive technologies. METHODS: Data were generated through registries and compared to pregnancies in Denmark in 1995. Those pregnancies that resulted in a delivery were compared to a matched control group. RESULTS: In 1994 and 1995 5219 women were treated in 9471 initiated cycles. The numbers increased over the period. The overall delivery rate per initiated cycle was 19%, egg donation 24%, IVF 20%, ICSI 16% and frozen egg replacement 10%. The rates increased over the period. The rate of spontaneous abortions was highest for ICSI (25%) and egg donation (27%). For IVF and ICSI the birth rates per transfer of 1 embryo was 13, 1%, 2 embryos 25, 4%, 3 embryos 25, 8% and 4 or more 3, 8%. Transfer of 2 embryos resulted in 75% singleton, 25% twin and 0.2% triplet deliveries. After transfer of 3 embryos the corresponding rates were 68%, 29% and 4%. No quadruplet deliveries occurred. Totally, 1.4% reported complications to the treatment, the most frequent being ovarian hyperstimulation syndrome. In the study group 5.8% of the women who gave birth were diagnosed with imminent abortion vs. 3.0% in the control group (OR 1.98, CI 1.41-2.78). CONCLUSIONS: Transfer of three embryos did not result in higher pregnancy rates as compared to transfer of two embryos. The first data from the Danish IVF Registry support data from other registries regarding treatment, pregnancy outcome and complications during pregnancy.

Oocyte donation in women cured of cancer with bone marrow transplantation including total body irradiation in adolescence.

Female survivors of cancer in childhood and adolescence who have been treated with bone marrow transplantation including total body irradiation (TBI) are at high risk of developing ovarian follicular depletion and infertility. The lack of oocytes may be compensated for by oocyte donation but these patients also seem to have a uterine factor. Even though oestrogen replacement therapy is given, the growth of the uterus during adolescence is impaired. To our knowledge there have been no earlier reports of live births after oocyte donation in such patients. We report three cases of oocyte donation in women who, at a young age, were cured of haematological malignancies with bone marrow transplantation including TBI. In adolescence they developed ovarian failure and uterine volumes were assessed by ultrasonography. One woman with a uterus of almost normal size delivered a healthy child in the 37th week of gestation. Another woman with severely diminished uterine volume miscarried in the 17th week of gestation. The third woman has not yet conceived. Pregnancy achieved by oocyte donation is possible despite TBI in adolescence. However, the uterine factor is a concern and complications during pregnancy and preterm birth may be expected in these patients.