Essure (Bayer) received approval from the U.S. Food and Drugs Administration as a permanent non-hormonal contraceptive implant in November 2002. While the use of Essure in the management of hydrosalpinx prior to in vitro fertilization (IVF) remains off-label, it has been used specifically for this purpose since at least 2007. Although most published reports on Essure placement before IVF have been reassuring, clinical experience remains limited, and no randomized studies have demonstrated the safety or efficacy of Essure in this context. In fact, no published guidelines deal with patient selection or counseling regarding the Essure procedure specifically in the context of IVF. Although Essure is an irreversible birth control option, some patients request the surgical removal of the implants for various reasons. While these patients could eventually undergo hysterectomy, at present no standardized technique exists for simple Essure removal with conservation of the uterus. This article emphasizes new aspects of the Essure procedure, as we describe the first known association between the placement of Essure implants and the subsequent development of fluid within the uterine cavity, which resolved after the surgical removal of both devices.
Endometrial fluid; Essure; Fertilization in vitro; Hydrosalpinx; Laparoscopy
The ability of the resistance elicitors acibenzolar-S-methyl (ASM), β-aminobutyric acid (BABA), cis-jasmone (CJ), and a combination of the three products, to control infection of spring barley by Rhynchosporium commune was examined under glasshouse conditions. Significant control of R. commune was provided by ASM and CJ, but the largest reduction in infection was obtained with the combination of the three elicitors. This elicitor combination was found to up-regulate the expression of PR-1b, which is used as a molecular marker for systemic acquired resistance (SAR). However, the elicitor combination also down-regulated the expression of LOX2, a gene involved in the biosynthesis of jasmonic acid (JA). In field experiments over 3 consecutive years, the effects of the elicitor combination were influenced greatly by crop variety and by year. For example, the elicitor combination applied on its own provided significant control of powdery mildew (Blumeria graminis f.sp. hordei) and R. commune in 2009, whereas no control on either variety was observed in 2007. In contrast, treatments involving both the elicitor combination and fungicides provided disease control and yield increases which were equal to, and in some cases better than that provided by the best fungicide-only treatment. The prospects for the use of elicitor plus fungicide treatments to control foliar pathogens of spring barley in practice are discussed.
Blumeria graminis f.sp. hordei; disease control; elicitors; induced resistance; Rhynchosporium commune; systemic acquired resistance
To measure Irish opinion on a range of assisted human reproduction (AHR) treatments.
A nationally representative sample of Irish adults (n=1,003) were anonymously sampled by telephone survey.
Most participants (77%) agreed that any fertility services offered internationally should also be available in Ireland, although only a small minority of the general Irish population had personal familiarity with AHR or infertility. This sample finds substantial agreement (63%) that the Government of Ireland should introduce legislation covering AHR. The range of support for gamete donation in Ireland ranged from 53% to 83%, depending on how donor privacy and disclosure policies are presented. For example, donation where the donor agrees to be contacted by the child born following donation, and anonymous donation where donor privacy is completely protected by law were supported by 68% and 66%, respectively. The least popular (53%) donor gamete treatment type appeared to be donation where the donor consents to be involved in the future life of any child born as a result of donor fertility treatment. Respondents in social class ABC1 (58%), age 18 to 24 (62%), age 25 to 34 (60%), or without children (61%) were more likely to favour this donor treatment policy in our sample.
This is the first nationwide assessment of Irish public opinion on the advanced reproductive technologies since 2005. Access to a wide range of AHR treatment was supported by all subgroups studied. Public opinion concerning specific types of AHR treatment varied, yet general support for the need for national AHR legislation was reported by 63% of this national sample. Contemporary views on AHR remain largely consistent with the Commission for Assisted Human Reproduction recommendations from 2005, although further research is needed to clarify exactly how popular opinion on these issues has changed. It appears that legislation allowing for the full range of donation options (and not mandating disclosure of donor identity at a stipulated age) would better align with current Irish public opinion.
Assisted fertility; Legislation; Public policy; In vitro fertilization; Ireland
To report on relationships among baseline serum anti-Müllerian hormone (AMH) measurements, blastocyst development and other selected embryology parameters observed in non-donor oocyte IVF cycles.
Pre-treatment AMH was measured in patients undergoing IVF (n = 79) and retrospectively correlated to in vitro embryo development noted during culture.
Mean (+/- SD) age for study patients in this study group was 36.3 ± 4.0 (range = 28-45) yrs, and mean (+/- SD) terminal serum estradiol during IVF was 5929 +/- 4056 pmol/l. A moderate positive correlation (0.49; 95% CI 0.31 to 0.65) was noted between basal serum AMH and number of MII oocytes retrieved. Similarly, a moderate positive correlation (0.44) was observed between serum AMH and number of early cleavage-stage embryos (95% CI 0.24 to 0.61), suggesting a relationship between serum AMH and embryo development in IVF. Of note, serum AMH levels at baseline were significantly different for patients who did and did not undergo blastocyst transfer (15.6 vs. 10.9 pmol/l; p = 0.029).
While serum AMH has found increasing application as a predictor of ovarian reserve for patients prior to IVF, its roles to estimate in vitro embryo morphology and potential to advance to blastocyst stage have not been extensively investigated. These data suggest that baseline serum AMH determinations can help forecast blastocyst developmental during IVF. Serum AMH measured before treatment may assist patients, clinicians and embryologists as scheduling of embryo transfer is outlined. Additional studies are needed to confirm these correlations and to better define the role of baseline serum AMH level in the prediction of blastocyst formation.
serum AMH; IVF; embryo development; blastocyst transfer
This analysis reports on Irish regulatory policies for in vitro fertilisation (IVF) from 2004-2009, in the context of membership changes within the Medical Council of Ireland. To achieve this, the current (2009) edition of the Guide to Professional Conduct & Ethics was compared with the immediately preceding version (2004). The statutory composition of the Medical Council from 2004-2009 was also studied. Content analysis of the two editions identified the following differences: 1) The 2004 guide states that IVF "should only be used after thorough investigation has failed to reveal a treatable cause of the infertility", while the 2009 guide indicates IVF "should only be used after thorough investigation has shown that no other treatment is likely to be effective"; 2) The 2004 stipulation stating that fertilized ovum (embryo) "must be used for normal implantation and must not be deliberately destroyed" is absent from the 2009 guidelines; 3) The option to donate "unused fertilised ova" (embryos) is omitted from the 2009 guidelines; 4) The 2009 guidelines state that ART should be offered only by "suitably qualified professionals, in appropriate facilities, and according to the international best practice"; 5) The 2009 guidelines introduce criteria that donations as part of a donor programme should be "altruistic and non-commercial". These last two points represent original regulatory efforts not appearing in the 2004 edition. The Medical Practitioners Act 2007 reduced the number of physicians on the Medical Council to 6 (of 25) members. The ethical guidelines from 2004 preceded this change, while the reconstituted Medical Council published the 2009 version. Between 2004 and 2009, substantial modifications in reproductive health policy were incorporated into the Medical Council's ethical guidelines. The absence of controlling Irish legislation means that patients and IVF providers in Ireland must rely upon these guidelines by default. Our critique traces the evolution of public policy on IVF during a time when the membership of the Medical Council changed radically; reduced physician contribution to decision-making was associated with diminished protection for IVF-derived embryos in Ireland. Considerable uncertainty on IVF practice in Ireland remains.
Guidelines for safe gamete donation have emphasised donor screening, although none exist specifically for testing oocyte recipients. Pre-treatment assessment of anonymous donor oocyte IVF treatment in Ireland must comply with the European Union Tissues and Cells Directive (Directive 2004/23/EC). To determine the effectiveness of this Directive when applied to anonymous oocyte recipients in IVF, we reviewed data derived from selected screening tests performed in this clinical setting.
Data from tests conducted at baseline for all women enrolling as recipients (n = 225) in the anonymous oocyte donor IVF programme at an urban IVF referral centre during a 24-month period were analysed. Patient age at programme entry and clinical pregnancy rate were also tabulated. All recipients had at least one prior negative test for HIV, Hepatitis B/C, chlamydia, gonorrhoea and syphilis performed by her GP or other primary care provider before reproductive endocrinology consultation.
Mean (±SD) age for donor egg IVF recipients was 40.7 ± 4.2 yrs. No baseline positive chlamydia, gonorrhoea or syphilis screening results were identified among recipients for anonymous oocyte donation IVF during the assessment interval. Mean pregnancy rate (per embryo transfer) in this group was 50.5%.
When tests for HIV, Hepatitis B/C, chlamydia, gonorrhoea and syphilis already have been confirmed to be negative before starting the anonymous donor oocyte IVF sequence, additional (repeat) testing on the recipient contributes no new clinical information that would influence treatment in this setting. Patient safety does not appear to be enhanced by application of Directive 2004/23/EC to recipients of anonymous donor oocyte IVF treatment. Given the absence of evidence to quantify risk, this practice is difficult to justify when applied to this low-risk population.
This investigation describes features of patients undergoing in vitro fertilisation (IVF) and embryo transfer (ET) where both gametes were obtained from anonymous donors.
Gamete unsuitability or loss was confirmed in both members of seven otherwise healthy couples presenting for reproductive endocrinology consultation over a 12-month interval in Ireland. IVF was undertaken with fresh oocytes provided by anonymous donors in Ukraine; frozen sperm (anonymous donor) was obtained from a licensed tissue establishment. For recipients, saline-enhanced sonography was used to assess intrauterine contour with endometrial preparation via transdermal estrogen.
Among commissioning couples, mean±SD female and male age was 41.9 ± 3.7 and 44.6 ± 3.5 yrs, respectively. During this period, female age for non dual anonymous gamete donation IVF patients was 37.9 ± 3 yrs (p < 0.001). Infertility duration was ≥3 yrs for couples enrolling in dual gamete donation, and each had ≥2 prior failed fertility treatments using native oocytes. All seven recipient couples proceeded to embryo transfer, although one patient had two transfers. Clinical pregnancy was achieved for 5/7 (71.4%) patients. Non-transferred cryopreserved embryos were available for all seven couples.
Mean age of females undergoing dual anonymous donor gamete donation with IVF is significantly higher than the background IVF patient population. Even when neither partner is able to contribute any gametes for IVF, the clinical pregnancy rate per transfer can be satisfactory if both anonymous egg and sperm donation are used concurrently. Our report emphasises the role of pre-treatment counselling in dual anonymous gamete donation, and presents a coordinated screening and treatment approach in IVF where this option may be contemplated.
Premature ovarian failure (POF) remains a clinically challenging entity because in vitro fertilisation (IVF) with donor oocytes is currently the only treatment known to be effective.
A 33 year-old nulligravid patient with a normal karyotype was diagnosed with POF; she had a history of failed fertility treatments and had an elevated serum FSH (42 mIU/ml). Oocytes donated by her dizygotic twin sister were used for IVF. The donor had already completed a successful pregnancy herself and subsequently produced a total of 10 oocytes after a combined FSH/LH superovulation regime. These eggs were fertilised with sperm from the recipient's husband via intracytoplasmic injection and two fresh embryos were transferred to the recipient on day three.
A healthy twin pregnancy resulted from IVF; two boys were delivered by caesarean section at 39 weeks' gestation. Additionally, four embryos were cryopreserved for the recipient's future use. The sister-donor achieved another natural pregnancy six months after oocyte retrieval, resulting in a healthy singleton delivery.
POF is believed to affect approximately 1% of reproductive age females, and POF patients with a sister who can be an oocyte donor for IVF are rare. Most such IVF patients will conceive from treatment using oocytes from an anonymous oocyte donor. This is the first report of births following sister-donor oocyte IVF in Ireland. Indeed, while sister-donor IVF has been successfully undertaken by IVF units elsewhere, this is the only known case where oocyte donation involved twin sisters. As with all types of donor gamete therapy, pre-treatment counselling is important in the circumstance of sister oocyte donation.
This study sought to describe patient features before beginning fertility treatment, and to ascertain their perceptions relative to risk of twin pregnancy outcomes associated with such therapy.
Data on readiness for twin pregnancy outcome from in vitro fertilisation (IVF) was gathered from men and women before initiating fertility treatment by anonymous questionnaire.
A total of 206 women and 204 men were sampled. Mean (± SD) age for women and men being 35.5 ± 5 and 37.3 ± 7 yrs, respectively. At least one IVF cycle had been attempted by 27.2% of patients and 33.9% of this subgroup had initiated ≥3 cycles, reflecting an increase in previous failed cycles over five years. Good agreement was noted between husbands and wives with respect to readiness for twins from IVF (77% agreement; Cohen's K = 0.61; 95% CI 0.53 to 0.70).
Most patients contemplating IVF already have ideas about particular outcomes even before treatment begins, and suggests that husbands & wives are in general agreement on their readiness for twin pregnancy from IVF. However, fertility patients now may represent a more refractory population and therefore carry a more guarded prognosis. Patient preferences identified before IVF remain important, but further studies comparing pre- and post-treatment perceptions are needed.
This study assessed pharmacy performance and satisfaction as reported by patients during ovulation induction therapy.
Materials and methods
Patients (n = 1269) receiving gonadotropin prescriptions for intrauterine insemination or in vitro fertilisation-embryo transfer in 2007–2008 were prospectively interviewed by nurses and/or completed a structured questionnaire to evaluate pharmacy performance. "Community" (n = 12) and "specialty" (n = 2) pharmacy status (C vs. S) was defined by each pharmacy, and all pharmacies were selected by patients before cycle start. Patient comments about their pharmacy were classified into five types: i) Dispensing error-gonadotropin, ii) Dispensing error-non gonadotropin, iii) Mistake in prescribed medical equipment/supplies, iv) Counselling/communication inaccuracy, and v) Inventory problem or other.
391 pharmacy concerns were reported from 150 fertility patients during the study period. The majority (75.9%) of patients selected a S pharmacy to fill their prescriptions, and this pharmacy type was identified in 2.8% of adverse pharmacy encounters (p < 0.0001). Non-gonadotropin prescriptions filled at C pharmacies accounted for 40.2% of all complaints, followed by problems with prescriptions for supplies (20.2%) and gonadotropins (18.7%) at C pharmacies. Patient conflict involving S pharmacies was limited (n = 11), and related to operating hours and medication delivery logistics.
Fertility patients reported a disproportionate and significantly higher number of adverse pharmacy encounters from C pharmacies compared to S pharmacies. Although no licensing mechanism in Ireland currently recognises special training or certification in any area of pharmacy practice, informal self-designations by pharmacies remain a useful discriminator. Level of familiarity with fertility medicines and availability of inventory are important characteristics to be considered when counselling fertility patients about pharmacy choice. Those who select a C pharmacy should be advised to allow extra time for inventory verification, order confirmation, and additional counselling. Additional study is needed to determine if a minimum volume of fertility-related prescriptions is necessary to assure competence in this particular field of pharmacy practice.
To present a diagnostic evaluation and treatment strategy for serous adenocarcinoma of the ovary discovered during an in vitro fertilisation (IVF) sequence, and report on reproductive outcome after tumour resection and embryo transfer.
Cycle monitoring in IVF identified an abnormal ovarian lesion which was subjected to ultrasound-guided needle aspiration. Cytology suggested malignancy, and unilateral oophorectomy was performed after formal staging. After surgery, the patient underwent an anonymous donor oocyte IVF cycle which established a viable twin intrauterine pregnancy. No recurrence of cancer has been detected in the >72 month follow-up interval; mother and twin daughters continue to do well.
Suspicious adnexal structures noted during controlled ovarian hyperstimulation for IVF warrant assessment, and this report confirms the role of aspiration cytology in such cases. If uterine conservation is possible, successful livebirth can be achieved from IVF if donor oocyes are utilised, as described here.
To review utilisation of elective embryo cryopreservation in the expectant management of patients at risk for developing ovarian hyperstimulation syndrome (OHSS), and report on reproductive outcome following transfer of thawed embryos.
Materials and methods
Medical records were reviewed for patients undergoing IVF from 2000–2008 to identify cases at risk for OHSS where cryopreservation was electively performed on all embryos at the 2 pn stage. Patient age, total number of oocytes retrieved, number of 2 pn embryos cryopreserved, interval between retrieval and thaw/transfer, number (and developmental stage) of embryos transferred (ET), and delivery rate after IVF were recorded for all patients.
From a total of 2892 IVF cycles undertaken during the study period, 51 IVF cases (1.8%) were noted where follicle number exceeded 20 and pelvic fluid collection was present. Elective embryo freeze was performed as OHSS prophylaxis in each instance. Mean (± SD) age of these patients was 32 ± 3.8 yrs. Average number of oocytes retrieved in this group was 23 ± 8.7, which after fertilisation yielded an average of 14 ± 5.7 embryos cryopreserved per patient. Thaw and ET was performed an average of 115 ± 65 d (range 30–377 d) after oocyte retrieval with a mean of 2 ± 0.6 embryos transferred. Grow-out to blastocyst stage was achieved in 88.2% of cases. Delivery/livebirth rate was 33.3% per initiated cycle and 43.6% per transfer. Non-transferred blastocysts remained in cryostorage for 24 of 51 patients (46.1%) after ET, with an average of 3 ± 3 blastocysts refrozen per patient.
OHSS prophylaxis was used in 1.8% of IVF cycles at this institution; no serious OHSS complications were encountered during the study period. Management based on elective 2 pn embryo cryopreservation with subsequent thaw and grow-out to blastocyst stage for transfer did not appear to compromise embryo viability or overall reproductive outcome. For these patients, immediate elective embryo cryopreservation and delay of ET by as little as 30 d allowed for satisfactory conclusion of the IVF sequence, yielding a livebirth-delivery rate (per ET) >40%.