Biomedical subjects

N S Macklon

Publications and source records attributed to N S Macklon.

At least 19 recordsLinked to original sources

PubMed2006

[Pregnancy at a later age with the help of oocyte donation].

An increasing number of women are delaying childbirth until an age when their fertility has significantly declined. Oocyte donation provides the opportunity for women to successfully conceive regardless of age. In The Netherlands, in 1997 the age limit for oocyte donation treatment was set at 45 years. The most important objections to pregnancy in older women are the medical risks for mother and child, the application of fertility treatments beyond the natural reproductive age and the psychosocial consequences for the child. However, based on international experience and recent data concerning the risks of pregnancy after oocyte donation in older women, it is proposed to increase the maximum age limit for this procedure to 50 years.

Female↗

PubMed2006

ART: iatrogenic multiple pregnancy?

Assisted reproductive technologies (ART) are now widely accepted as effective treatment for most causes of infertility. With improving success rates, attention has turned to the problem of multiple pregnancies, which are associated with a poor perinatal outcome, maternal complications and significant financial consequences. The challenge is to reduce multigestational pregnancies while maintaining good treatment outcomes. Methods to prevent multiple pregnancy include restrictive use of ART in couples with a good chance of spontaneous pregnancy, cautious use of gonadotrophins, and increased use of natural-cycle intra-uterine insemination and elective single embryo transfer in in-vitro fertilization and intracytoplasmic sperm injection. The aim of this article is to review the contribution of fertility treatment to multiple pregnancies and strategies for reducing multiples in ART.

Embryo Transfer↗

PubMed2006

A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common reproductive disorder associated with many characteristic features, including hyperandrogenaemia, insulin resistance and obesity which may have significant implications for pregnancy outcomes and long-term health of the woman. This meta-analysis was conducted to evaluate the risk of pregnancy and neonatal complications in women with PCOS. Electronic databases were searched for the following MeSH headings: PCOS, hyperandrogenism, pregnancy outcome, pregnancy complications, diabetes mellitus, type II. A handsearch of human reproduction and fertility and sterility was also conducted. Studies in which pregnancy outcomes in women with PCOS were compared with controls were considered for inclusion in this meta-analysis. Fifteen of 525 identified studies were included, involving 720 women presenting with PCOS and 4505 controls. Women with PCOS demonstrated a significantly higher risk of developing gestational diabetes [odds ratio (OR) 2.94; 95% confidence interval (CI): 1.70-5.08], pregnancy-induced hypertension (OR 3.67; 95% CI: 1.98-6.81), pre-eclampsia (OR 3.47; 95% CI: 1.95-6.17) and preterm birth (OR 1.75; 95% CI: 1.16-2.62). Their babies had a significantly higher risk of admission to a neonatal intensive care unit (OR 2.31; 95% CI: 1.25-4.26) and a higher perinatal mortality (OR 3.07; 95% CI: 1.03-9.21), unrelated to multiple births. In conclusion, women with PCOS are at increased risk of pregnancy and neonatal complications. Pre-pregnancy, antenatal and intrapartum care should be aimed at reducing these risks.

Birth Weight↗

PubMed2006

Implantation of the human embryo: research lines and models. From the implantation research network 'Fruitful'.

Infertility is an increasing problem all over the world, and it has been estimated that 10-15% of couples in fertile age have fertility problems. Likewise induced unsafe abortion is a serious threat to women's health. Despite advances made in assisted reproduction techniques, little progress has been made in increasing the success rate during fertility treatment. This document describes a wide range of projects carried out to increase the understanding in the field of embryo implantation research. The 'Fruitful' research network was created to encourage collaborations within the consortium and to describe our different research potentials to granting agencies or private sponsors.

Animals↗

PubMed2006

Optimum number of oocytes for a successful first IVF treatment cycle.

Ovarian stimulation in IVF allows selection of embryos for transfer, but may have detrimental effects on oocyte and embryo quality and endometrial receptivity. This study investigated the optimal response to ovarian stimulation in terms of number of oocytes for achieving pregnancy in a first IVF cycle. Data from 7422 women who underwent their first IVF cycle for standard indications were analysed. All had been treated with exogenous gonadotrophins and gonadotrophin releasing hormone (GnRH) agonist co-treatment in a long down-regulation protocol between 1990 and 1995. Pregnancy rates in relation to the number of obtained oocytes were adjusted for age, fecundity, subfertility cause, gonadotrophin dosage, type of luteal support, and number of transferred embryos by multivariate analysis. Of the 7422 women who underwent oocyte retrieval, overall 85% had an embryo transfer and 24% conceived. The highest pregnancy rates per embryo transfer and per started cycle were observed when 13 oocytes were obtained (31 and 28%, respectively). This study supports the concept of an optimal range of oocytes obtained in response to ovarian stimulation for IVF, below and above which outcomes are compromised.

Adolescent↗

PubMed2006

What can the clinician do to improve implantation?

Implantation is a complicated process that requires the orchestration of a series of events involving both the embryo and the endometrium. Even with the transfer of high quality embryos, implantation rates remain relatively low. The growing tendency towards transferring fewer embryos provides further incentives to improve implantation rates. In this article, the various clinical strategies employed to increase the chance of implantation are reviewed. Embryo transfer technique is a critical step in assisted reproductive technology cycles. Recent studies have shown significant improvements in clinical pregnancy rates resulting from careful embryo transfer technique, appropriate catheter type and placing for embryo transfer. Increasingly, adjuvant pharmaceutical therapies are also being applied with the aim of improving embryo implantation. However, the evidence for their efficacy and safety is limited. Recent evidence suggests that adoption of milder ovarian stimulation regimens may provide a more effective clinical approach to improving implantation, since beneficial effects have been shown for both endometrial receptivity and embryo quality.

Aromatase Inhibitors↗

PubMed2005

The psychological impact of mild ovarian stimulation combined with single embryo transfer compared with conventional IVF.

BACKGROUND: The objective of this study was to assess the psychological implications of mild ovarian stimulation combined with single embryo transfer (SET) during a first IVF cycle. METHODS: We conducted a randomized controlled two-centre trial. Three hundred and ninety-one couples were randomized to undergo either mild ovarian stimulation with GnRH antagonist co-treatment and SET (n=199) or conventional GnRH agonist long protocol ovarian stimulation with double embryo transfer (DET) (n=192). Women completed the Hospital Anxiety and Depression Scale, the Hopkins Symptom Checklist and the Subjective Sleep Quality Scale at baseline, on the first day of ovarian stimulation and following embryo transfer. Affect was assessed daily with the Daily Record Keeping Chart from the first day of ovarian stimulation until the day treatment outcome became known. RESULTS: The conventional IVF group experienced elevated levels of physical and depressive symptoms during pituitary downregulation. At oocyte retrieval, this group experienced more positive affect and less negative affect than the mild IVF group. In the conventional IVF group, cycle cancellation was associated with less positive and more negative affect. CONCLUSIONS: During the first IVF treatment cycle, mild ovarian stimulation and SET does not lead to more psychological complaints than conventional IVF.

Anxiety↗

PubMed2005

Preimplantation genetic screening reveals a high incidence of aneuploidy and mosaicism in embryos from young women undergoing IVF.

BACKGROUND: In order to assess the frequency of aneuploidy and mosaicism in embryos obtained from IVF patients aged <38 years, preimplantation genetic screening (PGS) was performed after biopsy of two blastomeres. Furthermore, the reliability of this diagnosis was assessed by performing reanalysis of the embryo on day 5. METHOD: The copy numbers of 10 chromosomes (1, 7, 13, 15, 16, 18, 21, 22, X and Y) were investigated by fluorescence in situ hybridization (FISH) analysis. Embryos that were found to be abnormal or of insufficient morphological quality were cultured until day 5 and reanalysed. Results obtained were compared to the day 3 blastomere analysis. RESULTS: After analysis of 196 embryos (one cell in 38% and two cells in 62%), only 36% of the embryos were found to be normal on day 3. After analysis of two blastomeres, 50% showed chromosomal mosaicism. Comparison of the FISH results from day 3 blastomeres and day 5 embryos yielded an overall cytogenetic confirmation rate of 54%. CONCLUSIONS: The rates of mosaicism and aneuploidy in these embryos from young IVF patients are similar to those published for older women. We found the best confirmation rate after a diagnosis based on two cells, where both blastomeres showed the same chromosomal abnormality. In contrast, after a mosaic diagnosis the confirmation rate was low. The present study provides the first detailed reanalysis data of embryos analysed by PGS and clearly demonstrates the impact of mosaicism on the reliability of the PGS diagnosis.

Adult↗

PubMed2005

A meta-analysis of outcomes of conventional IVF in women with polycystic ovary syndrome.

This meta-analysis was conducted to compare outcomes of conventional IVF in women presenting with polycystic ovary syndrome (PCOS) and non-PCOS patients. Studies in which PCOS patients undergoing IVF were compared with a matched--no male factor--control group were considered for this review. A definition consistent with the Rotterdam consensus criteria of PCOS was required, and all patients within a given study had to be treated with the same ovarian stimulation protocol. Information regarding patient characteristics and pregnancy outcome was also required. Nine out of 290 identified studies reporting data on 458 PCOS patients (793 cycles) and 694 matched controls (1116 cycles) fulfilled these inclusion criteria. PCOS patients demonstrated a significantly reduced chance of oocyte retrieval per started cycle, odds ratio (OR) = 0.5 [95% confidence interval (CI) = 0.2-1.0]. However, no difference was observed in chance of embryo transfer per oocyte retrieval between the groups (OR = 0.7, 95% CI = 0.4-1.3). Significantly more oocytes per retrieval were obtained in PCOS patients compared with controls [random effects estimate 3.4 [95% (CI) = 1.7-5.1)]. The number of oocytes fertilized did not differ significantly between PCOS patients and controls, weighted mean difference (WMD) 0.1 oocytes (95% CI = 21.4-1.6). No significant difference was observed in the clinical pregnancy rates per started cycle, OR = 1.0 (95% CI = 0.8-1.3). The incidence of ovarian hyperstimulation syndrome (OHSS) after oocyte retrieval was rarely reported. This meta-analysis demonstrates an increased cancellation rate, but more oocytes retrieved per retrieval and a lower fertilization rate in PCOS undergoing IVF. Overall, PCOS and control patients achieved similar pregnancy and live birth rates per cycle.

Female↗

PubMed2005

Effectiveness of a psychosocial counselling intervention for first-time IVF couples: a randomized controlled trial.

BACKGROUND: The objective of this study was to evaluate a psychosocial counselling intervention for first-time IVF couples. In this article the results on women's distress are presented. METHODS: Two hundred sixty-five couples admitted to an IVF treatment programme at the Erasmus MC were asked to participate in this study. Eighty-four couples agreed and were randomized according to a computer-generated random-numbers table into either a routine-care control group or an intervention group. The intervention consisted of three sessions with a social worker trained in Experiential Psychosocial Therapy: one before, one during and one after the first IVF cycle. Distress was measured daily during treatment by the Daily Record Keeping Chart. Depression and anxiety were measured before and after treatment by the Hospital Anxiety and Depression Scale. RESULTS: No significant group differences were found. CONCLUSIONS: The results of this study do not support the implementation of our counselling intervention for all first-time IVF couples. The low response rate suggests that there is little perceived need for psychosocial counselling among couples during a first IVF treatment cycle.

Adult↗

PubMed2005

Ovarian reserve.

The tendency to delay childbirth has increased the importance of ovarian reserve as a determinant of infertility treatment outcome. In the context of assisted reproduction technology, effective strategies to overcome the impact of ovarian aging and diminished ovarian reserve on pregnancy chances remain elusive. Markers of ovarian reserve are increasingly used to aid management and counseling of these patients. Proper interpretation of currently applied hormonal markers, ultrasound parameters, and hormone challenge tests requires an understanding of what constitutes and determines ovarian reserve. This article addresses these aspects and highlights recent developments in the field.

Aging↗

PubMed2004

What is the most relevant standard of success in assisted reproduction? The next step to improving outcomes of IVF: consider the whole treatment.

Changing the way in which successful IVF treatment is defined offers a tool to improve efficacy while reducing costs and complications of treatment. Crucial to this paradigm shift is the move away from considering outcomes in terms of the single IVF cycle, and towards the started IVF treatment as a whole. We propose the most informative end-point of success in IVF to be the term singleton birth rate per started IVF treatment (or per given time period) in the overall context of patient discomfort, complications and costs. These end-points are important not only for patients, but also for clinicians, health economists and policy makers. Such an approach would encourage the development of patient-friendly and cheaper stimulation protocols with less stress, discomfort and side effects. The combination of mild ovarian stimulation with single embryo transfer may provide the same overall pregnancy rate per total IVF treatment, achieved in the same amount of time for similar direct costs, but with reduced patient stress and discomfort, and the near complete elimination of multiple pregnancies. This would offer major health and indirect cost benefits. If IVF success rates were to be expressed in terms of delivery of a term single baby per IVF treatment (or in a given treatment period), the introduction of single embryo transfer on a large scale would be facilitated.

Embryo Transfer↗

PubMed2003

[Transfer of only a single embryo in in-vitro fertilisation].

In order to obtain high pregnancy rates per IVF cycle, ovarian stimulation is employed to produce multiple embryos. The best embryos are transferred into the uterus and the remainder are frozen for possible use in later cycles. Despite limiting the number of transferred embryos, more than half of all IVF babies are the result of multiple pregnancies. The associated morbidity and costs have led to calls for the adoption of single embryo transfer. New techniques such as pre-implantation genetic screening for aneuploidy have enabled better embryo selection with optimal chances of a healthy child. Milder ovarian stimulation protocols may further reduce the morbidity and costs of IVF cycles. Improved cryopreservation techniques should improve the chances of pregnancies in subsequent cycles using excess embryos. The definition of success in IVF should be changed from number of children per IVF cycle to number of children born after singleton pregnancies per IVF treatment started.

Adult↗

PubMed2003

Health-related quality of life in relation to gender and age in couples planning IVF treatment.

BACKGROUND: Specific subgroups of people planning IVF might be at risk of having more psychological or health-related problems. Identification of subgroups at risk may better enable allocation of appropriate counselling. METHODS: A group of 425 men and 447 women planning to undergo IVF treatment filled out a questionnaire. Four domains of health-related quality of life were measured, namely perceived emotional, physical, cognitive and social functioning. RESULTS: Young men and women (aged 21-30 years) planning IVF had more short-term social and emotional problems than people of the same age group in the general population. No substantial differences were found in cognitive and physical functioning for all age groups of men nor women planning IVF compared with the general population. A high level of irrational parenthood cognitions substantially accounted for a less optimal score on all the different domains of quality of life. These cognitions ('needing a child in order to live a happy life') were especially prevalent among younger women. CONCLUSIONS: Patients with high levels of irrational parenthood cognitions are at risk of a less optimal quality of life. A short cognitive counselling therapy is advised for patients with high levels of these cognitions.

Adult↗

PubMed2003

Mild stimulation in in vitro fertilization.

Current approaches to ovarian stimulation for in vitro fertilization (IVF) are aimed at optimizing the number of oocytes retrieved in a treatment cycle. This approach is not without risks. Moreover, as the true costs of multiple pregnancy become clearer, the need to produce multiple embryos for transfer is increasingly questioned. Increasing knowledge of the physiological mechanisms involved in follicular development and dominance has led to new strategies in ovarian stimulation for IVF. The clinical availability of GnRH antagonists allows the normal cycle to be harnessed and manipulated by mild interventions to produce sufficient oocytes for successful IVF treatment. Recent evidence suggests that oocyte quality after mild stimulation may be superior to that after conventional stimulation regimens.

Dose-Response Relationship, Drug↗

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↗

PubMed2002

The added value of embryo cryopreservation to cumulative ongoing pregnancy rates per IVF treatment: is cryopreservation worth the effort?

PURPOSE: To calculate the added benefit of a cryopreservation program to the cumulative ongoing pregnancy rate over a maximum of three cycles of IVF. METHODS: A total of 1251 couples beginning their first IVF treatment between January 1995 and December 1999 were evaluated. Ongoing pregnancies from fresh and subsequent cryopreserved embryo transfer cycles were analyzed. Pregnancies arising from the cryopreservation cycle were considered to augment the cumulative pregnancy rate when no ongoing pregnancy arose from the fresh embryo transfer cycle. RESULTS: The ongoing pregnancy rate per cryopreserved embryo transfer was 11.7%. The cumulative ongoing pregnancy rate following three successive started fresh IVF cycles was 42.5%. When pregnancies arising from the transfer of thawed cryopreserved embryos were included, the cumulative ongoing pregnancy rate increased to 43.8%, rising to 44.8% when extrapolated data from as yet unthawed embryos was included. CONCLUSIONS: When analyzed in these terms, the supplementary benefit of cryopreserving supranumerical embryos appears limited.

Adult↗

PubMed2002

A prospective randomized comparison of sequential versus monoculture systems for in-vitro human blastocyst development.

BACKGROUND: Extending the period of in-vitro culture to the blastocyst stage may improve implantation rates in IVF treatment. Recognition of the dynamic nature of early embryo metabolism has led to the development of commercially available sequential culture systems. However, their improved efficacy over monoculture systems remains to be demonstrated in prospective studies. METHODS: Embryos obtained from 158 women undergoing IVF treatment were randomized by sealed envelopes to culture in one of three systems: (A) culture for 5 days in our own monoculture medium (Rotterdam medium); (B) culture for 3 days in Rotterdam medium followed by 2 days in fresh Rotterdam medium; (C) culture for 5 days using the commercially available G1/G2 sequential culture system. RESULTS: There were no significant differences in blastulation, implantation or pregnancy rates between the three tested culture systems. CONCLUSION: The employed monoculture system is as effective as the G1/G2 sequential system for the culture of blastocysts for IVF.

Blastocyst↗