The most common reason that IVF is unsuccessful is the failure of embryos to implant.Although embryo abnormality may be responsible in many cases, problems relating to abnormalities in a woman's immune system may play a part in a significant proportion of these failures. Evidence is emerging that immunologic and immunophenotypic evidence of local and peripheral natural killer[NK] cell activation and T-helper 1[TH1] dominance may be associated with unexplained repeated embryo implantation failure.We have identified women with these problems and treated them with what we consider appropriate immunotherapy.We present our findings. Retrospective review. 284 women with at least 3 unexplained IVF failures had blood tests for NK assay and TH1/TH2 intracellular cytokine ratios,in addition to other tests fo recurrent embryo implantaion failure.NK abnormalities were treated with intravenous immunoglobulin[IVIg] 25G once between day 8-10 of superovulation, repeated if pregnancy test was positive.TH1/TH2 abnormality with raised TNFalpha: IL10 ratios were treated with antiTNFalpha drugs[Infliximab] 200-300mg before IVF. No abnormalities were found in 13 women.105 women had NK abnormality and had IVIg.9 out of 12 egg recipients[75%]so treated conceived.93 had IVF with own eggs[mean age=37.6yrs, mean no. failed IVF=6.4]-51[54.8%] coceived. 37 women[mean age=37.3yrs,mean no. failed IVF=6.6] had raised TNFalpha/IL10 ratios and were treated with Infliximab.2 out 4 egg recipients so treated[50%]conceived and 20 out of 33 treated with own eggs[60.6%]conceived.49 women have delivered and all babies are fine. A pregnancy rate in the region of 10% would be expected in women with similar IVF profiles. Women with repeated unexplained IVF failures seem to have a high incidence of abnormalities on immunological testing for NK assay and TH1 dominance.Immunotherapy with IVIg and anti TNFalpha drugs seem to improve IVF outcome.More research is however urgently needed on this area.

Objective: To investigate the possibility that children born after ICSI were at increased risk for neurodevelopmental delay.Design: Retrospective case-control study.Setting: IVF clinic.Patient(s): Fifty-eight singleton children born after ICSI and 38 normally conceived singleton children (controls), matched for relevant sociodemographic characteristics, from Australia and 208 case-patients and 221 controls from the United Kingdom.Main Outcome Measure(s): Antenatal and perinatal, and sociodemographic characteristics; physical health, including congenital abnormalities; and neurodevelopment by using the Griffiths scales of mental development.Result(s): Eighty-five percent of case-patients and 96% controls were assessed at a mean age of 13 months. Neurodevelopmental scores were similar in all children. Perinatal outcome was similar, apart from more caesarean sections in the case-patients. Rates of congenital anomalies were similar (5.6% among case-patients vs. 5.7% among controls). Children from fathers with oligozoospermia showed no extra problems. Children born after ICSI in the United Kingdom and Australia were similar.Conclusion(s): Children conceived after ICSI did not differ from their naturally conceived peers in physical health or development at ages up to 15 months.

Background There have been reports suggesting that children born after in-vitro fertilisation by intracytoplasmic sperm injection (ICSI) are at increased risk of neurodevelopmental delay. We have undertaken a case-control study of this issue.Methods We studied 208 singleton children conceived by ICSI and a control group of 221 normally conceived singleton children. Children were recruited from 22 fertility centres and local nurseries throughout the UK. Controls were selected to match cases as closely as possible for social class, maternal educational attainment, region, sex, and race. The primary outcome measure was neurodevelopmental scoring; secondary measures were perinatal outcomes, postnatal health, and congenital abnormalities. A single examiner assessed all the children.Findings A follow-up rate of 90% for the ICSI group was achieved at a mean age of 17 months. No difference between the study children and controls was found in mean neurodevelopmental scores (98.08 [SD 10.93] vs 98.69 [9.99]) or any subscales on the Griffiths' scales of mental development. Perinatal outcome was similar apart from a higher rate of caesarean section (73 [35.1%] vs 53 [24.0%], p=0.015) and a lower mean birthweight (3163 [SD 642] vs 3341 [606] g, p=0.013) in the study group. Rates of major congenital abnormality were also similar overall (ten [4.8%] study vs ten [4.5%] control), although there were significantly more congenital anomalies among children born to fathers with oligozoospermia than in other children.Interpretation This population study did not show any significant difference between children conceived after ICSI and their naturally conceived peers in terms of physical health and development.

As survival increases, patients with cystic fibrosis (CF) are often confronted with reproductive issues. Initial reports gave conflicting advice regarding the outcome of pregnancy in CF, However a recent large longitudinal study of pregnancies in CF women suggested that pregnancy has little impact on morbidity or mortality, Reduced fertility in CF women has been described, possibly due to thickened cervical mucus, and intrauterine insemination (IUI) has been used to overcome this. We report the first woman with CF, to our knowledge, to be successfully treated with IVF after repeated failed attempts at IUI.

International Journal of Gynecology & ObstetricsVolume 70, Issue S2 p. B72-B73 Sperm function A study of the relationship between sperm morphology and the incidence of ionophore-induced acrosome reaction Z. Rashid, Z. RashidSearch for more papers by this authorS. Fleming, S. FlemingSearch for more papers by this authorS. Fishel, S. FishelSearch for more papers by this authorS. Thornton, S. ThorntonSearch for more papers by this authorG. Ndukwe, G. NdukweSearch for more papers by this authorM. Aloum, M. AloumSearch for more papers by this authorJ. Hall, J. HallSearch for more papers by this author Z. Rashid, Z. RashidSearch for more papers by this authorS. Fleming, S. FlemingSearch for more papers by this authorS. Fishel, S. FishelSearch for more papers by this authorS. Thornton, S. ThorntonSearch for more papers by this authorG. Ndukwe, G. NdukweSearch for more papers by this authorM. Aloum, M. AloumSearch for more papers by this authorJ. Hall, J. HallSearch for more papers by this author First published: 10 December 2003 https://doi.org/10.1016/S0020-7292(00)85139-5AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume70, IssueS22000Pages B72-B73 RelatedInformation

Intracytoplasmic sperm injection is often successful for treatment of male infertility; over 20 000 children have been born as a result.1 This bypassing of natural barriers to sperm selection has raised concerns about the children conceived.2 We report a population control study of children born in the United Kingdom as a result of this treatment. Children between 12 and 24 months old who had been singleton births were identified from a list of couples who had received the treatment and their parents were invited to participate; 123 of 137 families (90%) agreed. Control children, conceived naturally, were recruited from associated nurseries (105/123) or were social peers of cases (18/123). Altogether, 123 children born after intracytoplasmic sperm injection (study children) and 123 control children were seen. Children were matched for social class, maternal educational level, region, sex, and race but not maternal age. Multiple births were excluded to avoid confounding factors. Primary outcome measures were developmental scoring on the Griffiths scales of mental development3 and rates of congenital abnormalities. The Griffiths scales are an objective method of assessing development which uses five subscales. All subscales …

Various compounds have been used in the attempt to improve sperm motility, including pentoxifylline (PF), a methylxanthine derivative. It has been postulated that PF, being a phosphodiesterase inhibitor, increases sperm kinematic parameters and the number of spermatozoa exhibiting hyperactivated motility by raising the intracellular content of cAMP, a molecule involved in the generation of sperm energy. However, it has not been clarified whether the biological effects of PF on sperm motility correlate with its ability to increase intracellular cAMP levels. To examine this relationship, the kinematic parameters, hyperactivation, and intracellular cAMP content were evaluated in motile spermatozoa, obtained by discontinuous. Percoll gradient and swim-up from 21 normozoospermic semen samples, incubated without and with PF for 0, 1, 2, and 4 h, PF increased beat cross frequency after 1 and 2 h of incubation, curvilinear velocity and lateral head displacement (ALH) after 4 h, and hyperactivation after 1, 2, and 4 h, and decreased linearity (LIN) after 1 h of incubation. The intracellular cAMP content of spermatozoa incubated with PF increased at all time-points examined. Both intracellular cAMP content and increase in hyperactivation in response to PF decreased with the length of incubation. In the absence of PF, cAMP content was unchanged and was correlated significantly only with ALH and the percentage of spermatozoa with hyperactivated motility, Following incubation with PF, cAMP content correlated with hyperactivation and all sperm kinematic parameters, with the exception of LIN and straightness. These findings suggest that the beneficial effects of PF on sperm kinematic parameters and hyperactivation are related to its ability to increase intracellular cAMP content.

The aim of the study was to evaluate the predictive value of the zona-free hamster egg penetration test (ZHEPT) for success in in-vitro fertilization (IVF) at various insemination concentrations ranging between 0.1 and >0.6 x 10(6)/ml. The ZHEPT was assessed using sperm samples from 87 couples undergoing IVF treatment. A similar test was simultaneously performed on the same semen sample following ionophore induction of the acrosome reaction (ZHEPTii test). Both the tests were poorly correlated with the fertilization rate of IVF at all the insemination concentrations except at >0.6 x 10(6)/ml, when there was good correlation between the ZHEPTii test and the fertilization rate. Following exclusion of two cases with an oocyte problem, further statistical analysis revealed that both the ZHEPT and ZHEPTii tests were poorly correlated with fertilization rate in IVF in this treatment group. This study suggests that the ZHEPT (with and without ionophore induction of the acrosome reaction) has a poor predictive value for the success of fertilization in IVF treatment at any insemination concentration.

Infertility affects at least 14% of the reproductive population worldwide. Modern technology can provide genetically related offspring to 80% of couples seeking treatment, and pregnancy to a further 10-15% using donated gametes. However, that only a small proportion is able to acquire suitable treatment, even in the West, highlights the social, economic and political difficulties surrounding available resources for assisted conception technology.Before 1992 approximately 95% of severe male-factor infertility cases were offered sperm donation - unacceptable in many cultures. Since the development of intracytoplasmic sperm injection (ICSI), 90-95% of male-factor cases can now be offered the chance of their own genetic offspring. The use of egg donation and of surrogacy further expands opportunities for infertile couples to have children. In the former the recipient gestates and delivers her child, albeit genetically unrelated to herself, whilst in the latter the commissioning couple can have their genetic offspring via host surrogacy These technologies remain ethically challenging.Developments in embryology technology have helped couples whose problem is one of implantation rather than conception, and this includes assisted hatching and zygote/embryo repair. The alliance of such technologies to the development of molecular genetics permits the biopsy of an eight- to ten-cell embryo for chromosome/genetics analysis on the extracted cells. This procedure has both social and economic advantages and makes it possible for couples to refrain from embarking on a pregnancy should the embryo carry a feared hereditary disorder.More recently, techniques to preserve germ cells, both mature and immature, and the potential in prepubertal male cancer sufferers for ipsigeneic germ cell repopulation offer considerable opportunity to preserve the fertility of these boys. The technique of oocyte grafting after cryopreservation provides similar opportunities for females of all ages. The inherited disease of mitochondrial deoxyribonucleic acid (DNA) cytopathies, passed on through the maternal line via the egg cytoplasm, poses serious health risks to offspring, including epilepsy, deafness, blindness and muscular atrophy. Potential developments in embryo/zygote micromanipulation could provide the opportunity to preserve the genetic complement of the parents, while protecting the future offspring from diseased cytoplasmic mitochondria. Similar technology might help those couples who are infertile as a result of habitual miscarriage, rather than any problem with conception and implantation per se.Hence, in the future: in vitro fertilization (IVF) and embryology technology will not only provide children for the subfertile, but will encroach on health and disease issues unrelated to infertility.

During 1995 and 1996 the first spermatid pregnancies were announced with both round spermatid (ROSI) and elongated spermatid (ELSI) injections. These publications were flanked by live births from ROSI in a number of animal species, with resulting offspring appearing normal, healthy and fertile. However, the live births in humans heralded a scientific and ethical debate on the clinical use of this technology; and in a number of countries nationwide moratoria prohibiting spermatid microinjection were enjoined. Concerns surrounded the biological condition of spermatids and clinical implications of utilizing an immature spermatozoon for conception. Nevertheless, case reports and a few scientific studies on human spermatid conception have been published in recent years, and further polemic on testicular histopathology and prognosis has ensued. This paper reviews the current arguments on the clinical use of ROSI and ELSI, and evaluates the biology of the main contributory components of a spermatozoon to the subsequent embryo, namely the genetic material, the microtubular organizing complex and the putative oocyte activating factor. We also consider the relevant testicular histopathology and likely outcome in the context of the current birth rate from ROSI and ICSI. We conclude by considering the way forward for infertile men who require this technology to become genetic fathers, and whether the time is now appropriate to consider clinical trials.

We report a novel method of rescuing empty follicle syndrome (EFS) and provide evidence that it is a drug-related problem rather than a clinical dysfunction. In a preliminary study we established that in EFS the serum beta-human chorionic gonadotrophin (beta-HCG) concentrations 36 h after HCG administration never exceeded 10 mIU/ ml. beta-HCG concentrations were thus used to confirm EFS when oocytes were not retrieved from one ovary after controlled ovarian hyperstimulation. The procedure was suspended leaving intact all follicles in the second, ovary. After confirmation of EFS, a second HCG from a different batch was administered and 36 h later mature oocytes were retrieved from the intact ovary, suggesting a fault with the HCG previously administered. Three patients have been treated in this way. In the first case, four out of five mature eggs were fertilized after intracytoplasmic sperm injection (ICSI) resulting in the transfer of three top grade (grade 1) embryos. In the second case all seven mature oocytes fertilized after in-vitro fertilization (IVF) and three grade 1 embryos were transferred resulting in a twin pregnancy, now delivered. In the third case, five out of nine oocytes were fertilized after ICSI and one out of the three treated with high insemination concentration IVF fertilized, resulting in the transfer of three ICSI embryos.

Objective: To evaluate the effectiveness of TV albumin in preventing severe ovarian hyperstimulation syndrome (OHSS) in patients at risk.Design: Retrospective review and data analysis.Setting: University-based tertiary referral center for assisted reproductive technologies (ART).Patient(s): Sixty women at high risk of developing severe OHSS after superovulation for ART.Intervention(s): One liter of albumin (4.5%) administered IV during oocyte retrieval and immediately afterward.Result(s): Of the 60 women who had prophylactic IV albumin, 5 (8%) developed severe OHSS, which led to hospitalization. Eight (13%) developed moderate OHSS. Forty-seven (78%) did not develop any symptoms. Four of the 5 women who developed severe OHSS had ET and 3 of them (75%) were pregnant (1 twin and 2 singletons).Conclusion(s): Intravenous albumin administered at oocyte retrieval does not prevent the occurrence of severe OHSS, especially in cases associated with pregnancy. It is important that clinicians are not lured into a false sense of security by the early report, full of promise, on the use of TV albumin to prevent severe OHSS. (C) 1997 by American Society for Reproductive Medicine.