Duration of luteal support after IVF is important, so why is there no consistency in practice? The results of a dynamic survey of practice in the United Kingdom.

Luteal support is considered as an essential component of IVF treatment following ovarian stimulation and embryo transfer. Several studies have consistently demonstrated a benefit of luteal support compared with no treatment and whilst a number of preparations are available, no product has been demonstrated as superior. There is an emerging body of evidence which suggests that extension of luteal support beyond biochemical pregnancy does not confer a benefit in terms of successful pregnancy outcome. We performed two surveys separated by 5 years of practice evolution, with the latter reporting on the use of luteal support in all IVF clinics in the UK. All clinics reported utilising luteal support with the majority favouring the use of Cyclogest 400 mg twice daily. In contrast, there was no consensus on the optimal duration of luteal support. Whilst 24% of clinics withdrew luteal support at biochemical confirmation of pregnancy, 40% continued treatment until 12 weeks gestation. Several clinics even extended luteal support beyond 12 weeks gestation. We observed no difference in practice based on the size of the IVF unit or treatment funding source. Although there was some change in practice between surveys in many clinics, there was no uniformity in the direction of change.

Duration of luteal support (DOLS) with progesterone pessaries to improve the success rates in assisted conception: study protocol for a randomized controlled trial.

BACKGROUND: Luteal support with progesterone is necessary for successful implantation of the embryo following egg collection and embryo transfer in an in-vitro fertilization (IVF) cycle. Progesterone has been used for as little as 2 weeks and for as long as 12 weeks of gestation. The optimal length of treatment is unresolved at present and it remains unclear how long to treat women receiving luteal supplementation. DESIGN: The trial is a prospective, randomized, double-blind, placebo-controlled trial to investigate the effect of the duration of luteal support with progesterone in IVF cycles. Following 2 weeks standard treatment and a positive biochemical pregnancy test, this randomized control trial will allocate women to a supplementary 8 weeks treatment with vaginal progesterone or 8 weeks placebo. Further studies would be required to investigate whether additional supplementation with progesterone is beneficial in early pregnancy. DISCUSSION: Currently at the Hewitt Centre, approximately 32.5% of women have a positive biochemical pregnancy test 2 weeks after embryo transfer. It is this population that is eligible for trial entry and randomization. Once the patient has confirmed a positive urinary pregnancy test they will be invited to join the trial. Once the consent form has been completed by the patient a trial prescription sheet will be sent to pharmacy with a stated collection time. The patient can then be randomized and the drugs dispensed according to pharmacy protocol. A blood sample will then be drawn for measurement of baseline hormone levels (progesterone, estradiol, free beta-human chorionic gonadotrophin, pregnancy-associated plasma protein-A, Activin A, Inhibin A and Inhibin B). The primary outcome measure is the proportion of all randomized women that continue successfully to a viable pregnancy (at least one fetus with fetal heart rate >100 beats/minute) on transabdominal/transvaginal ultrasound at 10 weeks post embryo transfer/12 weeks gestation (that is at the end of 8 weeks supplementary trial treatment). TRIAL REGISTRATION: ISRCTN05696887.

Antibodies to Chlamydia trachomatis in serum and peritoneal fluid of women with endometriosis.

The specifics of inflammation created by infection with Chlamydia trachomatis could be favourable to the genesis of endometriosis. To investigate this hypothesis, we studied the association between Chlamydia trachomatis specific IgG and IgA antibodies in serum and the peritoneal fluid of 51 women undergoing laparoscopic surgery. There was no significant difference between women with and without endometriosis with respect to the incidence of IgG and IgA in serum or the peritoneal fluid. The results of our preliminary study did not show any significant link between past infection with Chlamydia trachomatis and the presence of endometriosis.

A randomized controlled clinical trial of 2295 ultrasound-guided embryo transfers.

BACKGROUND: We wanted to test the hypothesis that using abdominal ultrasound at the time of embryo transfer to guide replacement, improved pregnancy rates by at least 5%. METHODS: An RCT in a large assisted conception unit. A pilot study and power calculation suggested that at least 2000 embryo transfers were required to demonstrate a difference of 5%, for a test with 80% power and Type 1 error 0.05. Randomization, data entry and analysis were arranged independently. Randomization was stratified for age and fresh/frozen embryo transfer. Analysis was by intention to treat. RESULTS: There was no difference in clinical pregnancy or live birth rates between the two groups. The clinical pregnancy rate for ultrasound-guided embryo transfer was 22% and for non-ultrasound-guided embryo transfer was 23% (odds ratio: 0.96; 95% confidence interval: 0.79-1.18). CONCLUSIONS: We set out to determine whether ultrasound-guided embryo transfer improved clinical pregnancy rates and live birth rates in assisted conception. We used an appropriately powered RCT design. We did not demonstrate a difference. This outcome is at odds with the UKs National Institute of Clinical Excellence recommendations for fertility treatment (Fertility Assessment and Treatment for People with Fertility Problems. London, UK: RCOG Press, 2004, 112.) which used a meta-analysis of four smaller trials (range 362-800 patients, totalling 2051 embryo transfers) to conclude that ultrasound should be offered. We suggest that the current Cochrane review should be updated with data from our trial and recommend that consideration is given to accounting for heterogeneity between the included trials.

Infertility after fertility-preserving surgery for cervical carcinoma: the next challenge for reproductive medicine?

Radical trachelectomy is an operation developed as an alternative to radical hysterectomy for patients with small-volume, early stage cervical cancer, who wish to retain their fertility. The body of the uterus is left in place, so that future pregnancies can occur. Patients who have undergone radical trachelectomy may face problems conceiving naturally and may request assisted conception. This article explains the operation and the difficulties that those working in reproductive medicine may face.

Relationship between serum human chorionic gonadotrophin levels and body mass index in women undergoing in vitro fertilisation cycles.

OBJECTIVE: To ascertain if serum concentrations following injection of human chorionic gonadotropin (hCG) influenced the outcome of in vitro fertilisation (IVF) treatment and correlated to body mass index (BMI). STUDY DESIGN: A prospective study conducted with the participation of 149 women undergoing IVF and/or intracytoplasmic sperm injection (ICSI) treatment at the regional IVF Unit in Liverpool, UK. The BMI of each individual was calculated and serum hCG concentrations were measured at 12 and 36 h following a subcutaneously (SC) injection of 5000 IU hCG. The main outcome measures were fertilisation rate and biochemical pregnancy rate. RESULTS: No correlation was found between serum hCG levels at 12 and 36 h with the number of oocytes retrieved or the number of oocytes fertilised. Furthermore, there was no correlation between BMI and hCG levels at 12 and 36 h following administration (Pearson's correlation coefficient: -0.23, -0.24, respectively). CONCLUSION: Our results suggest that the serum concentrations of hCG do not influence IVF outcome and that the serum levels of hCG achieved following administration do not correlate with the individual's BMI. Serum hCG concentration also does not correlate with number of oocytes collected or fertilisation rate.

An investigation of the effects of endometriosis on the proteome of human eutopic endometrium: a heterogeneous tissue with a complex disease.

The pathogenesis of endometriosis includes the proliferation of heterogeneous endometrial cells and their invasion into ectopic sites within the peritoneal cavity. This may be due to abnormalities of the eutopic endometrium itself, predisposing the cells to survive and implant ectopically. We investigated the applicability of 2-DE gels and peptide mass mapping to identify candidate endometrial proteins with a role in endometriosis. Despite the heterogeneous nature of endometrium, our results show that combining the analysis of 2-DE gels and peptide mass mapping yields consistent data. We identified dysregulated proteins in women with endometriosis which included: (i) molecular chaperones including heat shock protein 90 and annexin A2, (ii) proteins involved in cellular redox state, such as peroxiredoxin 2, (iii) proteins involved in protein and DNA formation/breakdown, including ribonucleoside-diphosphate reductase, prohibitin and prolyl 4-hydroxylase, and (iv) secreted proteins, such as apolipoprotein A1. These proteins have functions which suggest that they could play a role in the pathogenesis of endometriosis. This study demonstrated that 2-DE gel analysis and mass spectroscopic protein identification are suitable for the identification of proteins with candidate associations with endometriosis. These techniques should be used on a larger scale to identify endometriosis-related proteins, thus improving the understanding of this complex disease.

Cystic fibrosis screening in assisted reproduction.

PURPOSE OF REVIEW: The purpose of this review is to discuss the incidence of cystic fibrosis in the general population, in ethnically diverse populations and specifically in couples needing assisted reproduction caused by male factor subfertility. We review the current understanding of risks for reproductive couples and discuss ideal screening strategies. RECENT FINDINGS: In ethnically diverse populations, a large difference in clinical sensitivity and birth prevalence exists between the broad racial/ethnic groups examined. Extensive data clearly demonstrate the cost-effectiveness of cystic fibrosis screening. Testing for cystic fibrosis gene mutations is reliable and, with a 26-mutation panel, nearly 90% of possible severe mutations can be detected. To halve the incidence of cystic fibrosis in the community, by offering genetic testing of the fetus if both partners are carrier positive, may also be possible. SUMMARY: Recent guidelines suggest that all couples contemplating pregnancy should be informed of molecular screening for cystic fibrosis carrier status for purposes of genetic counselling. In ethnically diverse populations, ethnic-specific mutations should be included in the mutation panels.

Placement of a Malecot catheter to enable embryo transfer after radical trachelectomy.

OBJECTIVE: To describe the use of a Malecot catheter as a stent after radical trachelectomy (RT). DESIGN: Case report. SETTING: Assisted conception unit at a teaching hospital in the United Kingdom. PATIENT(S): A 36-year-old woman undergoing IVF after her cervix had been excised for cervical carcinoma. Previous attempts at embryo transfer (ET) had been very traumatic and required a transmyometrial transfer on one occasion. INTERVENTION(S): A Malecot catheter was inserted into the uterine cavity after a dilatation procedure had been performed and removed before ovarian stimulation. MAIN OUTCOME MEASURE(S): Ease of ET. RESULT(S): The subsequent ET was much more straightforward. CONCLUSION(S): This technique can facilitate ET after RT if the passage is found to be stenosed.

Do lunar phases affect conception rates in assisted reproduction?

OBJECTIVES: To assess the effect of the phases of the moon on pregnancy rates in humans following in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) treatment. DESIGN: Retrospective, observational study. SETTING: Reproductive Medicine Unit, Liverpool Women's Hospital. PATIENT: Complete data for all women undergoing assisted conception procedures over a period of 13 years (1995-2002). INTERVENTION: Assisted conception procedures--IVF and ICSI. MAIN OUTCOME MEASURES: Biochemical pregnancy that is positive pregnancy test result following embryo transfer. RESULTS: There was no significant effect of any lunar phase on the incidence of biochemical pregnancy (p-value 0.71). Age of the woman significantly affects the chances of pregnancy, (OR 0.95, 95% CI 0.91, 0.998, and p-value 0.04). The chances of pregnancy rises significantly with increase in the number of embryos replaced from 1 to 2 (OR 2.97, CI 1.36, 6.48, and p-value 0.01). CONCLUSION: Pregnancy rates in humans, following assisted conception, appears to be independent of the effect of the lunar phase during which embryo transfer is carried out.

Manual vacuum aspiration (MVA) in the management of first trimester pregnancy loss.

BACKGROUND: Manual vacuum aspiration is not widely used for the evacuation of retained products of conception in western Europe despite its well-proven success and safety record. Nor is there much information about its use under intravenous (systemic) analgesia or patient-controlled anaesthesia in modern settings. AIM: To evaluate the use of manual vacuum aspiration for the evacuation of retained products of conception under systemic analgesia or patient-controlled anaesthesia in the management of first trimester miscarriages. METHODS: Fifty-eight women with a diagnosis of first trimester miscarriage (42 missed and 16 incomplete miscarriages) were treated with manual vacuum aspiration under systemic analgesia or patient-controlled anaesthesia. Success rates and patient satisfaction and acceptability were recorded. RESULTS: Of the 58 women recruited, 42 underwent the procedure under systemic analgesia and 15 under patient-controlled sedation while 1 woman opted for general anaesthesia. Successful evacuation was achieved in all cases. Both analgesic methods were associated with high levels of patient satisfaction and acceptability. CONCLUSIONS: Manual vacuum aspiration is an option in the management of all first trimester pregnancy losses. Comparisons with other treatment options are indicated.

Can history, ultrasound, or ELISA chlamydial antibodies, alone or in combination, predict tubal factor infertility in subfertile women?

BACKGROUND: This study aimed to determine whether medical history, transvaginal ultrasound (TVU) or Chlamydia trachomatis antibody testing (CAT), alone or in combination, could provide a non-invasive, clinically useful screening test for predicting tubal factor infertility (TFI) in subfertile women. METHODS: Prior to tubal evaluation, relevant medical history, TVU findings, and enzyme-linked immunosorbent assay (ELISA) IgG CAT results were collected. Sensitivity, specificity, likelihood ratios (LR) and accuracy for predicting TFI, as determined by laparoscopy and dye hydrotubation, were calculated for each test alone, and in parallel and series combination. RESULTS: Thirty per cent (63/207) were diagnosed with TFI. The highest sensitivity (67%, 95% CI: 54-77) included any positive test, yet missed one in three women with TFI. The highest specificity (100%, 95% CI: 97-100) required all three tests positive, but identified only three women. Only the combination of CAT and TVU rated as a good clinical test, but confidence intervals were wide due to the small numbers affected. The combination of CAT or TVU and CAT alone reported the highest accuracy (73%, 95% CI: 66-78), misdiagnosing one in four women. CONCLUSION: Medical history, TVU appearances, and ELISA IgG CAT alone, or in combination, failed to predict accurately TFI in subfertile women.

A potential new use for gonadotropin-releasing hormone antagonists.

OBJECTIVE: To describe a potential new use of gonadotropin-releasing hormone (GnRH) antagonists. DESIGN: Case report. SETTING: Assisted conception unit at a teaching hospital in the United Kingdom. PATIENT(S): A 37-year-old woman undergoing in vitro fertilization (IVF) who accidentally stopped using GnRH agonists after starting ovarian stimulation. INTERVENTION(S): A GnRH antagonist was used to avoid a luteinizing hormone (LH) surge and hence "rescue" the cycle. RESULT(S): Successful oocyte retrieval was carried out, two embryos transferred, and a viable twin pregnancy ensued. CONCLUSION(S): This may be a new indication for the use of GnRH antagonists.

New challenges for gamete donation programmes: changes in guidelines are needed.

In the UK, the Human Fertilisation and Embryology Act 1990 prevents children born as a result of donor-assisted conception from gaining access to identifying information about their genetic origins. There is growing concern that current screening protocols regarding gamete donation are ill-suited, especially in relation to genetic disease. There are no guidelines addressing the issues of confidentiality that might arise if a disease emerges after insemination and establishment of pregnancy. Donors may become aware that they are at risk of a familial condition after they have donated gametes or recipients of donated gametes may become aware of a genetic illness in the resulting child. At present, there is no agreed method for allowing this information to be given to the donor or other recipients of gametes from that person. We suggest that these issues should be raised with donors, and appropriate counselling and predictive tests offered to them. Changes in regulations regarding gamete donation should be considered that accommodate recent and possible future developments in genetics. Furthermore, consideration should be given to the storage of samples of DNA from donors for the future provision of genetic information.

Peritoneal environment, cytokines and angiogenesis in the pathophysiology of endometriosis.

Endometriosis, defined by the presence of viable endometrial tissue outside the uterine cavity, is a common condition affecting 2-3% of women of reproductive age. Today, a composite theory of retrograde menstruation with implantation of endometrial fragments in conjunction with peritoneal factors to stimulate cell growth is the most widely accepted explanation. There is substantial evidence that immunological factors and angiogenesis play a decisive role in the pathogenesis of endometriosis. In women with endometriosis, there appears to be an alteration in the function of peritoneal macrophages, natural killer cells and lymphocytes. Furthermore, growth factors and inflammatory mediators in the peritoneal fluid, produced mainly by peritoneal macrophages, are altered in endometriosis, indicating a role for these immune cells and mediators in the pathogenesis of this disease.

Effect of interleukin-8 (IL-8), anti-IL-8, and IL-12 on endometrial cell survival in combined endometrial gland and stromal cell cultures derived from women with and without endometriosis.

OBJECTIVE: To study the affects of interleukin-8 (IL-8), anti-IL-8, and IL-12 on in vitro proliferation of endometrial cells. DESIGN: An in vitro study. SETTING: Department of Obstetrics and Gynecology, University of Aberdeen, UK. PATIENT(S): Women attending a fertility clinic. INTERVENTION(S): In vitro cell cultures using culture media supplemented with IL-8 (100 ng/mL, 200 ng/mL, and 500 ng/mL), IL-12 (1 ng/mL, 5 ng/mL, and 25 ng/mL), and anti-IL-8 (0.1 microg/mL, 1 microg/mL, 10 microg/mL). MAIN OUTCOME MEASURE(S): In vitro survival of dispersed endometrial cells (combined epithelial and glandular) at 5 and 9 days of culture. RESULT(S): There was a dose-dependent stimulatory effect of IL-8 on survival of cells. From women with and without endometriosis, IL-12 at 1 ng/mL significantly inhibited the survival of endometrial cells from women without endometriosis as compared with cells from women with endometriosis. At 1 microg/mL, anti-IL-8 significantly inhibited the survival of endometrial cells from women with endometriosis compared with cells from women without endometriosis on day 5 of culture. CONCLUSION(S): Our findings confirm the stimulatory effects of IL-8 and its possible role in the pathogenesis of endometriosis. The effects of IL-12 and anti-IL-8 on endometrial cell survival varied according to the disease state and the concentration of the cytokines. Future in vitro studies on the role of anti-IL-8 and IL-12 should aim to use a greater range of concentrations and a higher density of endometrial cells in cultures supplemented with monocytes.