Human Fertilisation and Embryology Authority

STUDY QUESTION: What are the European trends and developments in ART and IUI in 2014 as compared to previous years? SUMMARY ANSWER: The 18th ESHRE report on ART shows a continuing expansion of both treatment numbers in Europe and more variability in treatment modalities resulting in a rising contribution to the birth rates in most participating countries. WHAT IS KNOWN ALREADY: Since 1997, ART data generated by national registries have been collected, analysed by the European IVF-monitoring (EIM) Consortium and reported in 17 manuscripts published in Human Reproduction. STUDY DESIGN, SIZE, DURATION: Continuous collection of European data by the EIM for ESHRE. The data for treatments performed in 2014 between 1 January and 31 December in 39 European countries were provided by national registries or on a voluntary basis by clinics or professional societies. PARTICIPANTS/MATERIALS, SETTING, METHODS: From 39 countries and 1279 institutions offering ART services, a total of 776 556 treatment cycles, involving 146 148 with IVF, 362 285 with ICSI, 192 027 with frozen embryo replacement (FER), 15 894 with PGT, 56 516 with egg donation (ED), 292 with IVM and 3404 with frozen oocyte replacement (FOR) were reported. European data on IUI using husband/partner's semen (IUI-H) and donor semen (IUI-D) were reported from 1364 institutions offering IUI in 26 countries and 21 countries, respectively. A total of 120 789 treatments with IUI-H and 49 163 treatments with IUI-D were included. MAIN RESULTS AND THE ROLE OF CHANCE: In 14 countries (17 in 2013), where all institutions contributed to their respective national registers, a total of 291 235 treatment cycles were performed in a population of ~208 million inhabitants, corresponding to 1925 cycles per million inhabitants (range: 423-2978 per million inhabitants). After treatment with IVF the clinical pregnancy rates (PR) per aspiration and per transfer were marginally higher in 2014 than in 2013, at 29.9 and 35.8% versus 29.6 and 34.5%, respectively. After treatment with ICSI the PR per aspiration and per transfer were also higher than those achieved in 2013 (28.4 and 35.0% versus 27.8 and 32.9%, respectively). After FER with own embryos the PR continued to rise, from 27.0% in 2013 to 27.6% in 2014. After ED a similar trend was observed with PR reaching 50.3% per fresh transfer (49.8% in 2013) and 48.7% for FOR (46.4% in 2013). The delivery rates (DR) after IUI remained stable at 8.5% after IUI-H (8.6% in 2013) and at 11.6% after IUI-D (11.1% in 2013). In IVF and ICSI together, 1, 2, 3 and ≥4 embryos were transferred in 34.9, 54.5, 9.9 and in 0.7% of all treatments, respectively (corresponding to 31.4%, 56.3, 11.5% and 1% in 2013). This evolution in embryo transfer strategy in both IVF and ICSI resulted in a singleton, twin and triplet DR of 82.5, 17.0 and 0.5%, respectively (compared to 82.0, 17.5 and 0.5%, respectively, in 2013). Treatments with FER in 2014 resulted in a twin and triplet DR of 12.4 and 0.3%, respectively (versus 12.5 and 0.3% in 2013). Twin and triplet DR after IUI were 9.5 and 0.3%, respectively, after IUI-H (in 2013:9.5 and 0.6%) and 7.7 and 0.3% after IUI-D (in 2013: 7.5 and 0.3%). LIMITATION, REASONS FOR CAUTION: The method of data collection and reporting varies among European countries. The EIM receives aggregated data from various countries with variable levels of completeness. Registries from a number of countries have failed to provide adequate data about the number of initiated cycles and deliveries. As long as incomplete data are provided, the results should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: The 18th ESHRE report on ART shows a continuing expansion of treatment numbers in Europe. The number of treatments reported, the variability in treatment modalities and the rising contribution to the birth rates in most participating countries point towards the increasing impact of ART on reproduction in Europe. Being the largest data collection on ART, the report gives detailed information about ongoing developments in the field. STUDY FUNDING/COMPETING INTEREST(S): The study has no external funding and all costs are covered by ESHRE. There are no competing interests.

BACKGROUND: In vitro fertilization is associated with a high risk of multiple births, which is a direct consequence of the number of embryos transferred. However, other factors that contribute to the risk are not well defined. METHODS: Using the data base established by the Human Fertilization and Embryology Authority in the United Kingdom, we studied the factors associated with an increased risk of multiple births in 44,236 cycles in 25,240 women. The factors included the woman's age, the cause and duration of infertility, previous attempts at in vitro fertilization, previous live births, number of eggs fertilized, and number of embryos transferred. RESULTS: Older age, tubal infertility, longer duration of infertility, and a higher number of previous attempts at in vitro fertilization were all associated with a significantly decreased chance of a birth and of multiple births. Previous live birth was associated with an increased chance of a birth but not of multiple births. The higher the number of eggs fertilized, the higher the likelihood of a live birth. When more than four eggs were fertilized, there was no increase in the birth rate for women receiving three transferred embryos as compared with those receiving two, but there was a considerable increase in the rate of multiple births when three were transferred (odds ratio, 1.6; 95 percent confidence interval, 1.5 to 1.8). CONCLUSIONS: Among women undergoing in vitro fertilization, the chances of a live birth are related to the number of eggs fertilized, presumably because of the greater selection of embryos for transfer. When more than four eggs are fertilized and available for transfer, the woman's chance of a birth is not diminished by transferring only two embryos. Transferring more embryos increases the risk of multiple births.

BACKGROUND: The object of this study was to evaluate the efficacy of laser assisted hatching (LAH) of embryos on implantation and pregnancy rates of a selected group of infertility patients. METHODS: A total of 322 cycles using LAH was undertaken in our Centre between June 1998 and September 1999. Patients were offered LAH if they fell in either one or more of the following categories: (i) Patients over 37 years of age undergoing either IVF or intracytoplasmic sperm injection (ICSI) treatment cycles; (ii) patients with more than 2 previous treatment cycle failures; (iii) patients undergoing frozen embryo replacement cycles and (iv) women who were considered to be poor responders. The initial results of totally breaching the zona pellucida (total LAH; group 1) did not meet with our expectations. We subsequently modified the technique to thinning one area of the zona pellucida (partial LAH; group 2) and this thinned area was then extended to a quarter segment (quarter LAH; group 3). RESULTS: In group 1, the pregnancy rate was 14.6% with a clinical pregnancy rate of 5.2%. In group 2 the pregnancy rate was 20.9% with a clinical pregnancy rate of 18% and for patients in group 3 the pregnancy rate was 29.0% with a clinical pregnancy rate of 22.1%. CONCLUSIONS: Overall there was firm statistical evidence that the pregnancy and clinical pregnancy rates arising from quarter LAH were higher in comparison with partial and total LAH.

We have assessed the use of cetrorelix, a gonadotrophin releasing hormone (GnRH) antagonist, in conjunction with clomiphene citrate and gonadotrophin in 31 in-vitro fertilization (IVF)/gamete intra-Fallopian transfer (GIFT) cycles for 25 difficult responders. Group I included 18 poor responders (24 cycles) with no live birth in 23 previous IVF cycles with GnRH agonists. Group II included seven patients (seven cycles) with polycystic ovaries. Thirteen previous IVF/GIFT cycles with GnRH agonists had resulted in one live birth and three of these patients had developed ovarian hyperstimulation syndrome (OHSS). The treatment protocol involved a daily dose of clomiphene citrate 100 mg for 5 days and gonadotrophin injections from cycle day 2. Cetrorelix 0.25 mg/day was started when the leading follicle reached 14 mm. The outcome in both groups was favourable compared to previous treatment with GnRH agonists. In group I the abandoned cycle rate was 29 versus 57% (P = 0.06). More oocytes were produced (6.4 versus 4.7 oocytes/cycle) at a lower dose of follicle-stimulating hormone (FSH) (709 versus 1163 IU/oocyte; P = 0.08) and two live births resulted (11.8%). In group II fewer oocytes were produced (10.2 versus 14.5 oocytes/cycle), using a lower dose of gonadotrophin (170 versus 189 IU/oocyte) and resulted in one ongoing pregnancy. No patients experienced OHSS. This report is preliminary and a further controlled randomized study is required.

Journal Article More experiences with ICSI continued: Simplified recovery, preparation and cryopreservation of testicular spermatozoa Get access Ian Craft, Ian Craft London Gynaecology and Fertility Centre112A Harley Street, London W1N 1AF, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Marinos Tsirigotis Marinos Tsirigotis London Gynaecology and Fertility Centre112A Harley Street, London W1N 1AF, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Human Reproduction, Volume 10, Issue 7, 1 July 1995, Pages 1623–1626, https://doi.org/10.1093/oxfordjournals.humrep.a136142 Published: 01 July 1995

The technique of fine needle aspiration (FNA) may have a role as a reliable, quick and easy method of obtaining testicular tissue. Recent advances in the management of male subfertility and, in particular, the finding that spermatozoa recovered from the epididymis and testis can result in embryo generation after intracytoplasmic sperm injection (ICSI), question the traditional role of open testicular biopsy for the assessment of spermatogenesis. FNA of the testis was performed on 19 cases of male subfertility and histological and cytological preparations obtained were assessed by light microscopy. FNA provided intact testicular tubules adequate for the histological assessment of spermatogenesis in all cases. There was good correlation with the cytological preparations which gave an indication of the number of mature spermatozoa present. FNA should be considered as a simple alternative to open testicular biopsy in the current investigation of male subfertility and as a method of retrieving spermatozoa for assisted conception using ICSI.

In-vitro fertilization (IVF) by intracytoplasmic sperm injection (ICSI) with spermatozoa retrieved by percutaneous epididymal sperm aspiration (PESA) is a novel, simple and effective treatment for azoospermic men. In all, 38 azoospermic men had an IVF/PESA/ICSI cycle. A total of 42 cycles were performed. The aetiology of azoospermia was classified as failed vasectomy reversal (12 patients/16 cycles), inflammatory obstruction (five patients/five cycles), partial testicular failure (five patients/five cycles) and bilateral congenital absence of vas (16 patients/16 cycles). Adequate sperm preparations for ICSI were obtained from 38 of the 42 treatment cycles (90%). The mean fertilization rate was 32.7%, and fertilization occurred in 35 cycles (92.0%). Embryo transfer was performed in 13 out of 14 cycles (93%) in men with a failed vasectomy reversal, four out of five cycles in men with an inflammatory obstruction (80%), four out of four cycles in men with a partial testicular failure (100%), and 14 out of 15 cycles in men with a bilateral congenital absence of vas (93%). The overall pregnancy rate per two or three embryos transferred was 28.6 and 26.3% per treatment cycle respectively. The sperm parameters of the final pooled sperm aspirate preparations varied widely among the four aetiological groups. These parameters were of no value in predicting the fertilization or pregnancy rates (P > 0.05), and neither was the embryo cleavage rate.

BACKGROUND: In vitro fertilization is associated with a high risk of\nmultiple births, which is a direct consequence of the number of embryos\ntransferred. However, other factors that contribute to the risk are not well\ndefined. METHODS: Using the data base established by the Human Fertilization\nand Embryology Authority in the United Kingdom, we studied the factors\nassociated with an increased risk of multiple births in 44,236 cycles in\n25,240 women. The factors included the woman's age, the cause and duration of\ninfertility, previous attempts at in vitro fertilization, previous live\nbirths, number of eggs fertilized, and number of embryos transferred. RESULTS:\nOlder age, tubal infertility, longer duration of infertility, and a higher\nnumber of previous attempts at in vitro fertilization were all associated with\na significantly decreased chance of a birth and of multiple births. Previous\nlive birth was associated with an increased chance of a birth but not of\nmultiple births. The higher the number of eggs fertilized, the higher the\nlikelihood of a live birth. When more than four eggs were fertilized, there\nwas no increase in the birth rate for women receiving three transferred\nembryos as compared with those receiving two, but there was a considerable\nincrease in the rate of multiple births when three were transferred (odds\nratio, 1.6; 95 percent confidence interval, 1.5 to 1.8). CONCLUSIONS: Among\nwomen undergoing in vitro fertilization, the chances of a live birth are\nrelated to the number of eggs fertilized, presumably because of the greater\nselection of embryos for transfer. When more than four eggs are fertilized and\navailable for transfer, the woman's chance of a birth is not diminished by\ntransferring only two embryos. Transferring more embryos increases the risk of\nmultiple births.

STUDY QUESTION: Does a policy of elective freezing of embryos, followed by frozen embryo transfer result in a higher healthy baby rate, after first embryo transfer, when compared with the current policy of transferring fresh embryos? SUMMARY ANSWER: This study, although limited by sample size, provides no evidence to support the adoption of a routine policy of elective freeze in preference to fresh embryo transfer in order to improve IVF effectiveness in obtaining a healthy baby. WHAT IS KNOWN ALREADY: The policy of freezing all embryos followed by frozen embryo transfer is associated with a higher live birth rate for high responders but a similar/lower live birth after first embryo transfer and cumulative live birth rate for normal responders. Frozen embryo transfer is associated with a lower risk of ovarian hyperstimulation syndrome (OHSS), preterm delivery and low birthweight babies but a higher risk of large babies and pre-eclampsia. There is also uncertainty about long-term outcomes, hence shifting to a policy of elective freezing for all remains controversial given the delay in treatment and extra costs involved in freezing all embryos. STUDY DESIGN, SIZE, DURATION: A pragmatic two-arm parallel randomized controlled trial (E-Freeze) was conducted across 18 clinics in the UK from 2016 to 2019. A total of 619 couples were randomized (309 to elective freeze/310 to fresh). The primary outcome was a healthy baby after first embryo transfer (term, singleton live birth with appropriate weight for gestation); secondary outcomes included OHSS, live birth, clinical pregnancy, pregnancy complications and cost-effectiveness. PARTICIPANTS/MATERIALS, SETTING, METHODS: Couples undergoing their first, second or third cycle of IVF/ICSI treatment, with at least three good quality embryos on Day 3 where the female partner was ≥18 and <42 years of age were eligible. Those using donor gametes, undergoing preimplantation genetic testing or planning to freeze all their embryos were excluded. IVF/ICSI treatment was carried out according to local protocols. Women were followed up for pregnancy outcome after first embryo transfer following randomization. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 619 couples randomized, 307 and 309 couples in the elective freeze and fresh transfer arms, respectively, were included in the primary analysis. There was no evidence of a statistically significant difference in outcomes in the elective freeze group compared to the fresh embryo transfer group: healthy baby rate {20.3% (62/307) versus 24.4% (75/309); risk ratio (RR), 95% CI: 0.84, 0.62 to 1.15}; OHSS (3.6% versus 8.1%; RR, 99% CI: 0.44, 0.15 to 1.30); live birth rate (28.3% versus 34.3%; RR, 99% CI 0.83, 0.65 to 1.06); and miscarriage (14.3% versus 12.9%; RR, 99% CI: 1.09, 0.72 to 1.66). Adherence to allocation was poor in the elective freeze group. The elective freeze approach was more costly and was unlikely to be cost-effective in a UK National Health Service context. LIMITATIONS, REASONS FOR CAUTION: We have only reported on first embryo transfer after randomization; data on the cumulative live birth rate requires further follow-up. Planned target sample size was not obtained and the non-adherence to allocation rate was high among couples in the elective freeze arm owing to patient preference for fresh embryo transfer, but an analysis which took non-adherence into account showed similar results. WIDER IMPLICATIONS OF THE FINDINGS: Results from the E-Freeze trial do not lend support to the policy of electively freezing all for everyone, taking both efficacy, safety and costs considerations into account. This method should only be adopted if there is a definite clinical indication. STUDY FUNDING/COMPETING INTEREST(S): NIHR Health Technology Assessment programme (13/115/82). This research was funded by the National Institute for Health Research (NIHR) (NIHR unique award identifier) using UK aid from the UK Government to support global health research. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR or the UK Department of Health and Social Care. J.L.B., C.C., E.J., P.H., J.J.K., L.L. and G.S. report receipt of funding from NIHR, during the conduct of the study. J.L.B., E.J., P.H., K.S. and L.L. report receipt of funding from NIHR, during the conduct of the study and outside the submitted work. A.M. reports grants from NIHR personal fees from Merck Serono, personal fees for lectures from Merck Serono, Ferring and Cooks outside the submitted work; travel/meeting support from Ferring and Pharmasure and participation in a Ferring advisory board. S.B. reports receipt of royalties and licenses from Cambridge University Press, a board membership role for NHS Grampian and other financial or non-financial interests related to his roles as Editor-in-Chief of Human Reproduction Open and Editor and Contributing Author of Reproductive Medicine for the MRCOG, Cambridge University Press. D.B. reports grants from NIHR, during the conduct of the study; grants from European Commission, grants from Diabetes UK, grants from NIHR, grants from ESHRE, grants from MRC, outside the submitted work. Y.C. reports speaker fees from Merck Serono, and advisory board role for Merck Serono and shares in Complete Fertility. P.H. reports membership of the HTA Commissioning Committee. E.J. reports membership of the NHS England and NIHR Partnership Programme, membership of five Data Monitoring Committees (Chair of two), membership of six Trial Steering Committees (Chair of four), membership of the Northern Ireland Clinical Trials Unit Advisory Group and Chair of the board of Oxford Brain Health Clinical Trials Unit. R.M. reports consulting fees from Gedeon Richter, honorarium from Merck, support fees for attendance at educational events and conferences for Merck, Ferring, Bessins and Gedeon Richter, payments for participation on a Merck Safety or Advisory Board, Chair of the British Fertility Society and payments for an advisory role to the Human Fertilisation and Embryology Authority. G.S. reports travel and accommodation fees for attendance at a health economic advisory board from Merck KGaA, Darmstadt, Germany. N.R.-F. reports shares in Nurture Fertility. Other authors' competing interests: none declared. TRIAL REGISTRATION NUMBER: ISRCTN: 61225414. TRIAL REGISTRATION DATE: 29 December 2015. DATE OF FIRST PATIENT’S ENROLMENT: 16 February 2016.

A total of 37 percutaneous epididymal sperm aspiration (PESA) and/or testicular sperm aspiration (TESA) procedures were performed under local anaesthesia (LA) on 34 men between June and November 1996. Local anaesthesia was achieved by injecting 10 ml of 1% lignocaine solution along the sides of the vas deferens near the external inguinal ring (spermatic cord block). Sperm retrieval was successful in 92% of the procedures. Of the 37 procedures, in 29 the patients felt either no pain or mild discomfort while in six they experienced moderate but tolerable pain. Analgesia was incomplete in two procedures and was supplemented with i.v. sedation. Vasovagal reflex in two procedures was reversed by i.v. atropine. In 24 procedures patients felt relaxed, whilst in 13 they felt anxious. In 32 procedures the patients expressed overall satisfaction. If the procedure was to be repeated, after 29 procedures the patients requested LA again, while after four procedures they preferred i.v. sedation and after four were undecided. LA is adequate for PESA and TESA in a large proportion of patients. Prior discussion of LA technique with the patient is necessary. Back-up facilities for i.v. sedation and atropine should be available.

We report an intramural pregnancy following a difficult embryo transfer in a 31 year-old woman, having in-vitro fertilization and embryo transfer for tubal factor infertility. The creation of a 'false passage' at a previous instrumentation of the cervix may be implicated in the ectopic placement of embryos.

Journal Article Late intracytoplasmic sperm injection (ICSI) in in-vitro fertilization (IVF) cycles Get access Marinos Tsirigotis, Marinos Tsirigotis London Gynaecology and Fertility CentreCozens House, 112A Harley Street, London WIN 1AF, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Christopher Redgment, Christopher Redgment London Gynaecology and Fertility CentreCozens House, 112A Harley Street, London WIN 1AF, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Ian Craft Ian Craft London Gynaecology and Fertility CentreCozens House, 112A Harley Street, London WIN 1AF, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Human Reproduction, Volume 9, Issue 7, 1 July 1994, Page 1359, https://doi.org/10.1093/oxfordjournals.humrep.a138710 Published: 01 July 1994

OBJECTIVE: To evaluate the rate of recovery of spermatozoa from the epididymis using a percutaneous aspiration technique and to assess the fertilization rate following intracytoplasmic sperm injection (ICSI). PATIENTS AND METHODS: Forty-two patients with azoospermia underwent a total of 46 treatment cycles of in vitro fertilization (IVF) and ICSI. The sperm used for ICSI was retrieved percutaneously by fine-needle aspiration and syringe suction (percutaneous epididymal sperm aspiration, PESA) from the epididymis in 28 patients (mean age 34.9 years), over 32 cycles. Six patients underwent microsurgical sperm aspiration (MESA) and in the remaining eight patients, neither percutaneous aspiration nor MESA yielded suitable sperm and spermatozoa extracted from testicular biopsy were used. RESULTS: A total of 362 oocytes were collected and of those, 286 (79%) were subjected to ICSI. Of the injected oocytes, 49 (17.2%) were damaged, 138 (48.3%) achieved normal fertilization and, of those, 112 (81.2%) cleaved. A total of 67 embryos were transferred and 18 more were suitable for cryopreservation. Of the 25 cycles with embryo transfer, eight resulted in a pregnancy and of these, one miscarried. The pregnancy rate was 25% per cycle and 32% per embryo transfer. The implantation rate was 12%. CONCLUSIONS: This extensive series of PESA/ICSI cycles indicates that PESA can be used successfully to retrieve spermatozoa in patients with azoospermia. The technique is simple, cost-effective and is associated with fewer complications compared to an open microsurgical procedure.

BACKGROUND: Freezing all embryos, followed by thawing and transferring them into the uterine cavity at a later stage (freeze-all), instead of fresh-embryo transfer may lead to improved pregnancy rates and fewer complications during in vitro fertilisation and pregnancies resulting from it. OBJECTIVE: We aimed to evaluate if a policy of freeze-all results in a higher healthy baby rate than the current policy of transferring fresh embryos. DESIGN: This was a pragmatic, multicentre, two-arm, parallel-group, non-blinded, randomised controlled trial. SETTING: Eighteen in vitro fertilisation clinics across the UK participated from February 2016 to April 2019. PARTICIPANTS: Couples undergoing their first, second or third cycle of in vitro fertilisation treatment in which the female partner was aged < 42 years. INTERVENTIONS: If at least three good-quality embryos were present on day 3 of embryo development, couples were randomly allocated to either freeze-all (intervention) or fresh-embryo transfer (control). OUTCOMES: The primary outcome was a healthy baby, defined as a live, singleton baby born at term, with an appropriate weight for their gestation. Secondary outcomes included ovarian hyperstimulation, live birth and clinical pregnancy rates, complications of pregnancy and childbirth, health economic outcome, and State-Trait Anxiety Inventory scores. RESULTS: = 476). Of the couples randomised, 117 (19%) did not adhere to the allocated intervention. The rate of non-adherence was higher in the freeze-all arm, with the leading reason being patient choice. The intention-to-treat analysis showed a healthy baby rate of 20.3% in the freeze-all arm and 24.4% in the fresh-embryo transfer arm (risk ratio 0.84, 95% confidence interval 0.62 to 1.15). Similar results were obtained using complier-average causal effect analysis (risk ratio 0.77, 95% confidence interval 0.44 to 1.10), per-protocol analysis (risk ratio 0.87, 95% confidence interval 0.59 to 1.26) and as-treated analysis (risk ratio 0.91, 95% confidence interval 0.64 to 1.29). The risk of ovarian hyperstimulation was 3.6% in the freeze-all arm and 8.1% in the fresh-embryo transfer arm (risk ratio 0.44, 99% confidence interval 0.15 to 1.30). There were no statistically significant differences between the freeze-all and the fresh-embryo transfer arms in the live birth rates (28.3% vs. 34.3%; risk ratio 0.83, 99% confidence interval 0.65 to 1.06) and clinical pregnancy rates (33.9% vs. 40.1%; risk ratio 0.85, 99% confidence interval 0.65 to 1.11). There was no statistically significant difference in anxiety scores for male participants (mean difference 0.1, 99% confidence interval -2.4 to 2.6) and female participants (mean difference 0.0, 99% confidence interval -2.2 to 2.2) between the arms. The economic analysis showed that freeze-all had a low probability of being cost-effective in terms of the incremental cost per healthy baby and incremental cost per live birth. LIMITATIONS: We were unable to reach the original planned sample size of 1086 and the rate of non-adherence to the allocated intervention was much higher than expected. CONCLUSION: When efficacy, safety and costs are considered, freeze-all is not better than fresh-embryo transfer. TRIAL REGISTRATION: This trial is registered as ISRCTN61225414. FUNDING: ; Vol. 26, No. 25. See the NIHR Journals Library website for further project information.

The aetiology of cryptorchidism is still undiscernible in the majority of cases. It has long been argued that cryptorchidism reflects a primary testicular maldevelopment, where the contralateral scrotal testis also suffers from aspermatogenesis and low spermatogonia count. The aim of the study was to determine the reproductive outcome of ex-cryptorchid men with azoospermia post-orchidopexy after testicular sperm extraction (TESE) and intracytoplasmatic sperm injection (ICSI). In a retrospective analysis, we compared the sperm retrieval, fertilization, pregnancy and live birth rates after ICSI of consecutive ex-cryptorchid azoospermic patients (n = 15) undergoing TESE between Jan 2000 and Dec 2007 vs. non-cryptorchid azoospermic men (n = 142). Sperm retrieval rate of ex-cryptorchid men by TESE (66%) was comparable with non-cryptorchid men (47%) (p = 0.15) despite significantly higher FSH levels (30.7 +/- 25.4 vs. 17.9 +/- 14.8 respectively) (p = 0.018) and a more prevalent histopathology diagnosis of aspermatogenesis (75% vs. 40%, p = 0.046). Fertilization (43.3%), pregnancy (30%) and live birth (20%) rates after TESE-IVF-ICSI in the ex-cryptorchid group were not different from the non-cryptorchid group (48.7, 43 and 29%, p = 0.26, p = 0.21, p = 0.29 respectively). We conclude that the reproductive outcome of ex-cryptorchid men with azoospermia post-orchidopexy employing TESE-IVF-ICSI is comparable with non-cryptorchid azoospermic men.

In the UK, following many years of consultation and debate, Parliament passed the Human Fertilisation and Embryology Act in 1990. This introduced a system of detailed regulation of banks and clinics undertaking the storage and use of gametes and embryos in the UK. The law established the framework for the system and set up the Human Fertilisation and Embryology Authority (HFEA) to implement it from 1991. The HFEA is required to license and monitor centres which store or use donated gametes, and to provide them with guidelines in a Code of Practice. The Code of Practice contains guidance on practical clinical matters and also the HFEA's policy on a number of social and ethical issues. The regulatory system was set up to reassure the public, to protect the interests of potential children, patients and donors, and to promote good practice in fertility research and treatment. It works by consultation and cooperation between the HFEA and the scientists and clinicians being regulated, although sanctions do exist for use where needed. The HFEA is notable in regulating an area of medical practice in such a detailed way. It has established itself as an effective regulator and adviser, and has provided a basis for the development of policy in the field of fertility treatment.

Forty-five cases of ectopic pregnancy occurred after gamete intrafallopian transfer (32 cases) or in vitro fertilization (13 cases). Ultrasonography positively identified ectopic pregnancy in 33 cases (73.4%) and suggested the presence of one in 7 cases (15.6%). There were five false-negative results (11.1%). The incidence of rare types of ectopic pregnancy after assisted fertility procedures, such as ovarian, heterotopic, cervical and ectopic pregnancy, in patients who had undergone a previous salpingectomy was increased. Ultrasound scanning was used to monitor three cases of nonviable ectopic pregnancy; all three required no further treatment. In 14 cases of viable ectopic pregnancy the gestational sac was aspirated and injected with potassium chloride and methotrexate. In seven of those cases no further treatment was needed. Patients who conceive as a result of assisted fertility procedures should be scanned four to six weeks after the procedure or sooner if they are considered at high risk of developing an ectopic pregnancy or if the condition is symptomatic.

This review discusses the place of regulation in the transition from research to clinical practice in human assisted conception, with particular emphasis on the United Kingdom and the role of the Human Fertilisation and Embryology Authority (HFEA). A contrast is drawn between advances in other areas of medical practice, in which the evidence base is considerable, and in assisted conception, in which it is often weak. This comparison leads to the central issue: how to balance the needs of patients with the need to ensure safety and efficacy in the introduction of new techniques. Comfort is derived from biological considerations that indicate that early human embryos are remarkably resilient and adaptable to challenges to their physiology. Regulatory practice in other countries is considered briefly. The review concludes that there are no easy rules or answers in managing the transition from research into the clinic, but that bodies such as the HFEA have a responsibility to: (i) encourage research to widen the evidence base and (ii) err on the side of caution when faced with decisions on licensing new techniques.

In IVF, eggs and sperm are added together for fertilisation to occur whereas ICSI involves injecting a single sperm into each egg. ICSI is very effective where sperm count or swimming is poor (male infertility) but is slightly riskier than IVF in terms of health problems in children, although these risks are small. However, the risk of no eggs fertilising is higher for IVF compared to ICSI and couples undertaking fertility preservation, for example, before cancer treatment, usually only have time for one attempt. Using fertility preservation treatment cycle data reported to Human Fertilisation and Embryology Authority (HFEA), this study shows that ICSI results in higher number of fertilised eggs and embryos for storage or treatment compared to IVF. However, 19% of eggs are not used in ICSI treatment, so IVF appears to be better overall. Clinics should choose IVF or ICSI for fertility preservation depending on sperm characteristics rather than using ICSI for all.

Maternal serum alpha-fetoprotein (MSAFP), human chorionic gonadotropin (hCG), and unconjugated oestriol (UE3) are used as second-trimester screening markers for the detection of various fetal abnormalities. Previous studies have suggested that second-trimester MSAFP is consistently elevated after late first-trimester transabdominal multifetal pregnancy reduction (MFPR). The present study was undertaken to evaluate the levels of all three markers after early transvaginal MFPR. Maternal serum was examined for MSAFP, hCG, and UE3 at 16-18 weeks' gestation in 28 patients who underwent transvaginal MFPR at approximately 10 weeks' gestation. The mean interval between the reduction procedure and the screening test was 7.2 +/- 0.9 weeks. The mean MSAFP value in 24 patients carrying viable twins was 2.49 +/- 0.99 multiples of the median (MOM). Two patients had elevated MSAFP values: one in association with omphalocoele and the other in relation to an adverse pregnancy outcome. All but two patients had normal hCG values (mean 1.98 +/- 1.26 MOM). Two cases with elevated hCG were associated with an adverse pregnancy outcome. Unconjugated oestriol values were within the normal range in all patients (mean 1.69 +/- 0.61 MOM). These results suggest that early transvaginal MFPR, at approximately 10 weeks' gestation, does not appear to influence second-trimester MSAFP, hCG, and UE3 levels. The values of these markers may therefore be interpreted by using the same criteria as those for the general obstetric population.