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PubMed2005

Management of poor responders in IVF.

Correct controlled ovarian stimulation is of paramount importance in assisted reproductive technologies. Therefore, analysis of the ovarian reserve of the patient is mandatory to tailor the best ovarian stimulation regimen. When the ovarian reserve is reduced, the induction of a multifollicular growth remains a challenge. Several factors could be associated with reduced ovarian response. However, reduced ovarian reserve either in older patients or in young patients represents the most frequent aetiological factor. Whatever is the aetiology, one of the main problems is how to predict a reduced ovarian response, and although several tests have been suggested, no very accurate predictive test is available. A variety of different stimulation protocols have been suggested but the lack of any large-scale, prospective, randomized, controlled trials of the different management strategies and the lack of a uniform definition of the population may result in comparisons of heterogeneous groups of patients, making it difficult to draw any definitive conclusions. Natural cycle IVF may represent an easy and cheap approach in the management of this group of patients. Although no controlled large prospective randomized studies are available to compare the natural IVF procedure with ovarian stimulation IVF in poor responder patients, the efficacy of natural cycle IVF is hampered by high cancellation rates mainly due to untimely LH surge. The use of gonadotrophin-releasing hormone antagonists in the late follicular phase, which reduces the premature LH rise rate, and the improvements in laboratory conditions and fertilization techniques, increase the embryo transfer rates, making this procedure more cost-effective.

Female↗
PubMed2005

Live birth after IVF in a 46-year-old woman.

Pregnancies after IVF have been reported in women aged > or =44 years, but nobody older than 45 years at oocyte retrieval delivered. We report a case of birth of a healthy child after IVF in a 46-year-old infertile woman. Ovarian stimulation was performed with clomiphene citrate, 150 mg daily for 5 days. Three oocytes were retrieved and one embryo was replaced. The patient delivered a healthy male infant after Caesarean section at 39 weeks. A successful pregnancy after IVF with homologous oocytes can be achieved in women older than 45 years. At this age IVF is not a cost-effective treatment compared with oocyte donation, but it may be offered in countries in which gamete donation is forbidden.

Age Factors↗
PubMed2005

FISH screening of aneuploidies in preimplantation embryos to improve IVF outcome.

Preimplantation genetic diagnosis (PGD) has transformed the approach to the infertility patient in the IVF setting. Although the principal applications of PGD have been to prevent the transmission of sex-linked diseases, in time and with growing knowledge of the chromosomal abnormalities observed in preimplantation embryos, its applications have widened. Nowadays, apart from its implications in the prevention of transmission of chromosomal and genetic abnormalities, PGD is being used with increased frequency to improve the IVF outcome in patients with advanced maternal age (> or =38 years of age), recurrent miscarriage (> or =2 miscarriages), recurrent IVF failure (> or =3 failed IVF attempts) and severe male infertility. A high incidence of chromosomal abnormalities has been observed in these patient groups.

Abortion, Habitual↗
PubMedDate not supplied

A special path to parenthood: parent-child relationships in families giving birth to singleton infants through IVF.

Infertility and its treatment are increasingly viewed as public issues as well as a private concern. Treatments such as IVF draw on public resources and pose psychological and ethical dilemmas for the community. The current paper integrates findings from a prospective longitudinal study that assessed the quality of parenting in families conceiving through IVF from an attachment theory perspective. Seventy families who conceived singleton infants through IVF and a naturally conceiving control group of 63 couples were seen during pregnancy and at 4 and 12 months postpartum. Two observational procedures were used to assess maternal sensitivity to the baby, infant responsiveness and security of attachment at 4 and 12 months respectively. There were no IVF control group differences in maternal sensitivity at 4 months or in security of attachment at 12 months. Implications of the findings for clinicians and contemporary controversies requiring further research are discussed.

Aging↗
PubMed2005

Factors predicting IVF treatment outcome: a multivariate analysis of 5310 cycles.

The objective of this study was to analyse factors predicting live birth rate following IVF. A computerized database of 1928 women who underwent 5310 consecutive IVF cycles in a single IVF unit was evaluated. Data on the women's age, number of retrieved oocytes, performance of intracytoplasmic sperm injection (ICSI), aetiology of infertility, number of transferred embryos and option of choosing embryos for transfer were evaluated. There were 1126 pregnancies that resulted in 689 live births. Transferring two embryos doubled the chances of delivery compared with one embryo, but transferring three embryos was not significantly superior to two embryos. Moreover, following a three-embryo transfer, the multiple delivery rates were significantly higher (P < 0.01) compared with transferring two embryos. Optimal delivery rates were observed in women aged 26-30 years, with gradual decline with advanced age. The performance of ICSI resulted in higher delivery rates compared with conventional insemination. According to these data, the best live birth results following IVF treatment were achieved when the maternal age was 26-30 years, in couples with male factor infertility undergoing ICSI, and when two embryos were transferred.

Adolescent↗
PubMed2005

Treatment of recurrent IVF failure and human leukocyte antigen similarity by intravenous immunoglobulin.

This study sought to assess the efficacy of intravenous immunoglobulin (IVIg) in improving pregnancy rates and outcome, in a select group of patients with repeated IVF failure and human leukocyte antigen (HLA) similarity. Couples suffering from recurrent IVF failure, defined as at least seven attempts at embryo transfer with no successful implantations, who were found to share at least three HLA loci, and a negative cross-match test, were included in the study. The treatment consisted of two 30 g IVIg doses: one before oocyte retrieval, and a second as soon as a fetal pulse was identified on ultrasound. Ten couples comprised the study group. In total, these couples had undergone 98 IVF cycles with no successful pregnancies prior to initiation of the study. Following a total of 18 IVIg courses, seven women conceived, two women twice. Up to date, five women have delivered at least one live fetus, at 27 weeks or later. One woman is currently in the early third trimester of a twin pregnancy, and one woman had a late abortion at 19 weeks. The results suggest that couples with recurrent IVF failure and HLA similarity, may benefit from IVIg treatment.

Adult↗
PubMed2005

Changing genetic world of IVF, stem cells and PGD. A. Early methods in research.

Genetics proved essential to introduce IVF, preimplantation diagnosis (PGD) and embryo stem cells in the 1960s. Its small input in early years was confined to aspects such as timing follicle growth and ovulation. Modest understanding in the mid- to late 1980s, mostly on studies in mice, involved the actions of single genes and the balance between maternal and zygotic transcripts in preimplantation stages. Human IVF began after human oocytes were matured in vitro, and their meiotic chromosomes analysed. Their fertilization in vitro led to PGD and embryo stem cells. Unlike mouse embryos, most human embryos failed to implant, so the best had to be selected to improve IVF pregnancy rates. Initially, faster-growing embryos proved superior. Later, patterns of polarized nucleoli in pronuclei, the degree of blastomere fragmentation and growth of embryos in vitro to blastocysts provided excellent markers. Single cells could be isolated from embryos using micromanipulation. Stem cells from inner cell mass, a branch of IVF, differentiated into immortal stem cell lines in vitro if disaggregated. They formed virtually all body tissues in blastocysts cultured intact or when injected singly into recipient blastocysts. Later, the genetic controls of ES cell differentiation were assessed, together with factors switching them along specific differentiation pathways. Marker genes identified ES cells differentiating into various tissues.

Animals↗
PubMedDate not supplied

IVF: past and future.

The introduction of IVF into the New World had its roots in Robert Edwards' six-week fellowship at Johns Hopkins in 1965, when he and I made a systematic attempt to fertilize human oocytes in vitro. While fertilization was not claimed in the publication of the work done in 1965, a retrospective examination of published photos indicate that human fertilization was obtained at that time. Edwards and Steptoe achieved a term birth with IVF in 1978, and this stimulated the establishment of an IVF clinic in Norfolk, Virginia. Using ovarian stimulation in 1981, the first delivery in the New World took place. This led to a series of studies on the influence of ovarian stimulation on the normal menstrual cycle and resulted in the finding that with ovarian stimulation there are three response patterns: high, normal and low. It was shown that an LH surge does not occur in ovarian stimulation. This latter observation led to the discovery of the LH surge inhibiting factor. The Norfolk programme became involved in the societal impact of IVF through an invitation to the Vatican, the Ethical Committee of the American Fertility Society (later the American Society for Reproductive Medicine), a lawsuit for libel against the local newspaper, and other activities.

Female↗
PubMedDate not supplied

Cumulative pregnancy rate following IVF and intracytoplasmatic sperm injection with ejaculated and testicular spermatozoa.

The purpose of this study was to calculate the cumulative pregnancy rates of IVF cycles with ICSI using ejaculated or testicular spermatozoa. A computerized database for the IVF cycles with ICSI performed between January 1996 and December 1998 was utilized. Cycles with spermatozoa obtained after electro-ejaculation were excluded. A multifactorial analysis was performed to define the impact of different factors on the success rate of IVF and ICSI. During a 36-month period, 229 pregnancies were achieved by 643 couples using ejaculated spermatozoa, and 83 pregnancies by 167 couples who required testicular spermatozoa. The pregnancy rates (PR) per cycle, including all treatment cycles with ejaculated spermatozoa, remained similar during the first five consecutive cycles achieving a cumulative PR of 80.44%. The cumulative pregnancy rates for cycles with testicular spermatozoa showed a consistent rise during four consecutive treatments and reached 61.84%. The regression analysis of pregnancy rate showed that it was significantly positively correlated with oocyte fertilization rate (P = 0.02), and negatively correlated with maternal age (P = 0.03). Thus, according to the present results, couples with infertility who require IVF with ICSI should be offered at least five consecutive attempts if ejaculated spermatozoa are used, and at least four cycles whenever testicular spermatozoa are used.

Ejaculation↗
PubMed2000

One hundred and three concurrent IVF successes for donors and recipients who shared eggs: ethical and practical benefits of egg sharing to society.

Egg sharing is a form of egg donation where complete strangers can collaborate anonymously to overcome their involuntary childlessness. In a retrospective analysis, results of egg sharing treatments were analysed in 37 consecutive donors and 39 recipients who had achieved concurrent success following IVF treatment. The interval between being accepted onto the programme and receiving treatment was less than 6 months for most patients. Births of 103 infants are expected. Multiple pregnancy rates were high and equivalent in both the groups (donors 32.4%, recipients 25.6%) despite the original number of eggs available being halved at egg collection and equal numbers being allocated to donors and recipients. On average fewer than six eggs were required for the birth of each baby. More successes are expected in time as 33 couples (43.4%) have their excess embryos stored for future use. The programme avoided the need to advertise for donors. This had particular significance for members of minority ethnic groups. It is surmised that promotion of concurrent treatment of egg sharers and recipients will attract funds from insurance providers or health boards who are unimpressed by IVF treatments with indifferent success rates and runaway costs. In the event of such funds materializing, meagre NHS resources for IVF treatment could be better focused. Overall, the benefit derived from applying the simultaneous treatment of anonymous donors and recipients is so compelling as to make it the preferred IVF option for qualifying couples.

Journal Article↗
PubMed2001

Morphology of spermatozoa used in IVF and ICSI from oligozoospermic men.

The purpose of this study was to determine morphology in human spermatozoa from men with oligozoospermia and correlate with the fertilization rate, embryo score and pregnancy rate after IVF and intracytoplasmic sperm injection (ICSI) respectively. The study group consisted of 125 couples where the male partner suffered from oligozoospermia. Fifty of these had IVF (group A). Seventy-five couples in whom ICSI had been performed made up group B. Sperm samples were assessed according to the WHO manual. For each male, morphology of spermatozoa was judged according to Krüger's strict criteria, WHO criteria and the teratozoospermia index (TZI). Oocyte monitoring was carried out according to a long down-regulation protocol using gonadotrophin-releasing hormone, recombinant FSH and human chorionic gonadotrophin. Embryos were transferred on day 2 after fertilization, with a maximum of three embryos. This study demonstrated no correlation between any of the morphological assessments of spermatozoa and the fertilization rate, embryo score and pregnancy rate, either after IVF or ICSI. Morphology in human spermatozoa according to Krüger's strict criteria, WHO criteria and the TZI had no predictive value for the outcome after either IVF or ICSI.

Journal Article↗
PubMed2004

17 alpha-hydroxyprogesterone caproate versus intravaginal progesterone in IVF-embryo transfer cycles: a prospective randomized study.

One of the main issues in the management of IVF and embryo transfer techniques is to ensure adequate concentrations of progesterone. The aim of this prospective, randomized study was to compare the effectiveness of 17 alpha -hydroxyprogesterone caproate (17-HPC) administered intramuscularly and intra-vaginal progesterone in gel in luteal phase support in patients undergoing IVF-embryo transfer cycles. A total of 320 patients were randomly treated with either 17-HPC (341 mg i. m. every 3 days) or progesterone vaginal gel (90 mg daily). The inclusion criteria were the use of gonadotrophin-releasing hormone down-regulation and age <40 years. The outcome of IVF in both study groups was evaluated for implantation rate, biochemical pregnancy, clinical pregnancy, miscarriage, and ongoing pregnancy rate. The results of this study showed that 17-HPC conferred more benefit to IVF-embryo transfer cycles compared with intra-vaginal progesterone, as demonstrated by the results of most of the main outcome parameters considered. The data showed that 17-HPC administered every 3 days appears to be more effective in providing luteal support in comparison to intra-vaginal progesterone.

17 alpha-Hydroxyprogesterone Caproate↗
PubMed2002

Ovarian stimulation for IVF and endometrial receptivity--the missing link.

The contemporary approach to ovarian stimulation for IVF treatment results in supraphysiological concentrations of steroids during the follicular and luteal phases of the menstrual cycle. These sex steroids act directly and indirectly to mature the endometrium, influencing receptivity for implantation. Corpus luteum function is distinctly abnormal in IVF cycles, and therefore luteal support is widely used. Various reasons may underlie the defective luteal phase, including (i) ovarian hyperstimulation per se, (ii) gonadotrophin-releasing hormone (GnRH) analogue co-treatment and (iii) the use of human chorionic gonadotrophin (HCG) to induce final oocyte maturation. The recent introduction of GnRH antagonist co-treatment for the prevention of a premature LH rise during the late follicular phase allows for different approaches to ovarian stimulation for IVF. However, a recent meta-analysis showed that implantation rates may be compromised by using GnRH antagonists in currently employed regimens. The development of endometrium receptive to embryo implantation is a complex process and may be altered by inappropriate exposure to sex steroids in terms of timing, duration and magnitude. New approaches to the assessment of endometrial receptivity are now required. Novel approaches to ovarian stimulation aimed at adjusted GnRH antagonist regimens and achieving a more physiological luteal phase endocrinology are now appearing in the literature and may represent an important step in the improvement of the overall health economics of IVF.

Chorionic Gonadotropin↗
PubMed1999

The outcome of cryopreserved human embryos after intracytoplasmic sperm injection and traditional IVF.

OBJECTIVE: Our objective was to analyze the outcome of cryopreserved embryos obtained after intracytoplasmic sperm injection (ICSI) and in vitro fertilization (IVF) in terms of survival rate, implantation rate (IR), total and clinical pregnancy rate (PR) in a retrospective, comparative study. METHODS: Three hundred seventy-five IVF and 463 ICSI surnumerary cleaved embryos, frozen on Day 2 with 1,2-propanediol, were thawed. RESULTS: Thirty-two percent of the thawed IVF embryos survived and 11 pregnancies (8 clinical) were obtained from 68 transfers (16.1%). Fourty-seven percent of the ICSI embryos survived, with 19 pregnancies (18 clinical) from 116 transfers (16.4%). The IR was 8.5% (8/94) in IVF cycles and 10.8% (20/185) in ICSI cycles. CONCLUSIONS: A significantly better survival rate of ICSI embryos was observed but with no difference in PR, preclinical, and clinical abortion rate, or IR.

Adult↗
PubMed2002

Human chorionic gonadotropin combined with progesterone for luteal support improves pregnancy rate in patients with low late-midluteal estradiol levels in IVF cycles.

PURPOSE: To investigate how late-midluteal estradiol levels relate to the pregnancy outcome in IVF cycles, and to assess whether human chorionic gonadotropin (hCG) for luteal support benefits the pregnancy outcome of patients with low late-midluteal estradiol levels. METHODS: The pregnancy rate of 436 women undergoing first IVF cycles with long protocol and luteal support with progesterone alone were analyzed. Unsuccessful women with low late-midluteal estradiol levels (< 100 pg/mL) proceeded with the exploratory second IVF cycles where they were randomly given with either progesterone alone (P protocol) or hCG +progesterone (P+hCG protocol) for luteal support. RESULTS: Pregnancy rate in women with low late-midluteal estradiol levels was significantly lower compared to that with medium (100-500 pg/mL) and high (> 500 pg/mL) levels (13.3, 26.8, and 36.3%, respectively). P+hCG protocol increased late-midluteal estradiol levels and produced a significantly higher pregnancy rate (31.7%) than P protocol (13.7%). CONCLUSIONS: hCG in combination with progesterone for luteal support was suggested to benefit women undergoing IVF with low late-midluteal estradiol levels.

Adult↗
PubMed2003

Dilemma of increased obstetric risk in pregnancies following IVF-ET.

PURPOSE: To determine the rates of pregnancy complications following in vitro fertilization in comparison with those in a matched control group. METHODS: A total of 13,543 deliveries at the Department of Obstetrics and Gynecology, University of Szeged, between January 1, 1995 and February 28, 2002 were subjected to retrospective analysis The 230 (1.7%) pregnancies following IVF-ET were evaluated and matched with spontaneous pregnancies concerning age, parity, gravidity, and previous obstetric outcome. Demographic and selected maternal characteristics, pregnancy and labor complications, and neonatal outcome were compared in the two groups RESULTS: The pregnancy complication rate was partly significantly higher among the singleton IVF-ET pregnancies. The obstetric risk was elevated, though not significantly concerning twin pregnancies. CONCLUSIONS: IVF-ET presents an additional obstetric risk. The neonatal outcome displays a significant difference only concerning an increased premature birth rate of singleton pregnancies. Triplet IVF-ET pregnancies involve a much higher risk of both pregnancy complications and neonatal outcome.

Birth Weight↗
PubMed2001

IVF treatments and their outcomes in Finland in the 1990s.

BACKGROUND: In vitro fertilization and its variants have become routine infertility treatments in industrialized countries. Our purpose is to summarize the procedures and treatment outcomes in Finland in the 1990s and to compare the results between public and private clinics. METHODS: The data came from the Finnish IVF statistics for 1992 to 1999. Most analyses were done for the years 1994 to 1998 for which identical data-collection sheets were used. RESULTS: In 1999, 12 of the 19 clinics offering assisted reproductive treatments were private. The number of treatments increased from 2,331 in 1992 to 7,213 in 1999. In total 58% were performed in the private sector. Most treatments were given for women aged 30 to 39 years, but in the private sector women were up to on average two years older. Most often care was given due to tubal factor or unexplained infertility (IVF) and due to male factor or multiple causes (ICSI). The number of transferred embryos decreased during the study period, but the transfer of two embryos was still most frequent. Three out of four IVF and ICSI pregnancies, and two out of three FET pregnancies ended in a live birth. The success rates improved for IVF and for ICSI after adjustment for the number of transferred embryos, but not for FET. Small but inconsistent differences were observed in the success rates between the private and public sectors. There was noticeable variation between clinics. CONCLUSION: The number of treatment cycles stabilized in the late 1990s. The success rates improved only slightly and the differences in outcome measures between private and public clinics were small. However, neither this nor the large clinical variation could be investigated more thoroughly without collecting individual register data.

Adult↗
PubMed2006

The association between intron 4 VNTR, E298A and IVF 23+10 G/T polymorphisms of ecNOS gene and sildenafil responsiveness in patients with erectile dysfunction.

The objective of the study was to determine the association between intron 4 variable number of tandem repeats (VNTR), E298A and IVF 23+10 G/T polymorphisms of ec-NOS gene and sildenafil responsiveness in patients with erectile dysfunction (ED). Ninety-six patients who were evaluated for ED between November 2003 and June 2004 and 167 healthy individuals representing the normal population as controls were included in the present study. The patients were evaluated by medical history, five-item version of International Index of Erectile Function, serum glucose, testosterone levels and lipid profiles. Sixty-seven patients received four consecutive doses of sildenafil from 25 to 100 mg according to the response. The ec-NOS gene intron 4 VNTR, E298A and IVF 23+10 G/T polymorphisms were evaluated in the isolated DNA blood samples obtained from the patient group with ED (n=96), from the group received sildenafil (n=67) and from the healthy group (n=167). Genotype distributions of ec-NOS gene intron 4, E298A and IVF 23+10 G/T polymorphisms in the patient group were similar to those in the healthy group. The frequency of the ec-NOS gene intron 4 genotype were found as bb=41.7%, ab=50% and aa=8.3% in the sildenafil responders and bb=93.5% and ba=6.5% in the sildenafil non-responders. This finding was statistically significant. Statistical analysis of ec-NOS gene E298A and IVF 23+10 G/T polymorphisms did not reveal any significant difference between sildenafil responders and non-responders. These findings may indicate that 'a' allele of ec-NOS gene intron 4 VNTR polymorphism associates with a better sildenafil response.

3',5'-Cyclic-GMP Phosphodiesterases↗