Francisca Martínez

An analysis of factors associated with ectopic pregnancy in a human in vitro fertilization program

Between 1980 and 1985, in Monash University in vitro fertilization (IVF) program, ectopic pregnancy occurred in 10 of 256 IVF pregnancies. The incidence of ectopic pregnancy between 1983 and 1984 was 4% of the total pregnancies, or 4.2% of pregnancies excluding biochemical pregnancies. The incidence of ectopic pregnancy was distributed equally across the infertility classifications (tubal, idiopathic, male factor, and mixed). There appeared to be no relationship between superovulatory methods, endocrine changes before egg recovery, laparoscopic procedures, embryo transfer procedures, and number of embryos transferred. Nine of the ten patients were classified as having either tubal factor infertility before IVF or chronic tubal inflammation, which probably existed at the time of embryo replacement. No ectopic pregnancies were recorded in the 33 pregnancies obtained with superovulation with the use of clomiphene citrate alone. We were unable to identify a major predisposing factor for ectopic pregnancy in IVF.

Stimulation protocols for poor responders and aged women

There is a general consensus on the clinical fact that the more embryos replaced the higher pregnancy rates are achieved. For this reason those IVF cycles with a low response and a reduced number of oocytes and embryos will have very few chances of producing a pregnancy. It is very important to diagnose, by means of the anamnesis and hormonal tests which patients are most likely to present a poor response to conventional ovarian stimulation protocols. It is mandatory to know the patients plasmatic levels of FSH and estradiol together with personal data such as the age and the previous history of the patient. Only young poor responders with a normal basal hormonal profile will have some chances that by applying new protocols and combining new drugs, improve their response and have higher pregnancy rates. For the old poor responders who have already failed to alternative protocols including natural cycles, oocyte donation is the last and best hope.

Comparison of starting ovarian stimulation on day 2 versus day 15 of the menstrual cycle in the same oocyte donor and pregnancy rates among the corresponding recipients of vitrified oocytes

OBJECTIVE To assess the clinical pregnancy rate per transfer in recipients of embryos from donor oocytes obtained after ovarian stimulation initiated on day 2 (D2) or day 15 (D15) of the menstrual cycle with a secondary end point of comparing the response to stimulation. DESIGN Prospective observational comparative study. SETTING Private in vitro fertilization (IVF) program. PATIENT(S) Oocyte donors (OD) and recipients. INTERVENTION(S) Donors stimulated within 3 months, starting on day 2 or day 15 after bleeding, with recombinant follicle-stimulating hormone (FSH), gonadotropin-releasing hormone (GnRH) antagonist, and GnRH agonist trigger, and oocytes vitrified and later assigned to recipients, followed by routine IVF procedures one to two embryos transferred. MAIN OUTCOME MEASURE(S) Primary outcome pregnancy rate, and secondary outcome number of mature oocytes retrieved. RESULT(S) Nine D2 and nine D15 cycles were performed in nine donors. There were no differences between D2 and D15 in the number of mature oocytes obtained (14.0±6.96 vs. 16.89±7.52). To date, 20 recipients have received vitrified oocytes (8 recipients received D2 oocytes and 12 recipients received D15 oocytes). There were no differences between the groups of recipients in fertilization rate (77.3% vs. 76.5%) or number of embryos transferred (1.50±0.53 vs. 1.67±0.65). Twelve clinical pregnancies were obtained. No differences were noted in pregnancy rates (62.5% vs. 58.3%) or implantation rates (41.67% vs. 45%) between recipients of D2 oocytes and recipients of D15 oocytes. CONCLUSION(S) Donor oocytes obtained after ovarian stimulation initiated on day 15 of the cycle achieve good pregnancy rates. This information is useful for patients with cancer undergoing fertility preservation. CLINICAL TRIAL REGISTRATION NUMBER NCT 01645241.

Cancer and fertility preservation: Barcelona consensus meeting

Abstract Improvements in early diagnosis and treatment strategies in cancer patients have enabled younger women with cancer to survive. In addition to the stressful event of the diagnosis, patients with malignant diseases face the potential loss of the opportunity to have children. Preservation of fertility has become a challenging issue and it is still surrounded by controversies. On the basis of available evidence, a group of experts reached a consensus regarding the options for trying to preserve fertility in women with cancer: among established methods, in postpubertal women, oocyte cryopreservation is the preferred option, whereas ovarian tissue cryopreservation is the only possibility for prepubertal girls. Combining several strategies on an individual basis may improve the chances of success. Realistic information should be provided before any intervention is initiated. Counseling should offer support for patients and provide better care by understanding emotional needs, psychological predictors of distress and methods of coping. Early referral to the fertility specialist is essential as fertility preservation (FP) may improve quality of life in these patients. The information summarized here is intended to help specialists involved in the treatment of cancer and reproductive medicine to improve their understanding of procedures available for FP in young cancer patients.

Influence of spermatogenic profile and meiotic abnormalities on reproductive outcome of infertile patients

Genetic aspects of male infertility and the possible risks of new assisted reproduction and their influence on the development of zygotes and children born after intracytoplasmic sperm injection (ICSI) need further research. These patients have an increased risk of diploidy, and disomies are frequent in their spermatozoa. Meiotic disorders are more common in testicular biopsies of patients with severe oligoasthenozoospermia. For these reasons, a detailed andrological study is absolutely mandatory before accepting a couple with these characteristics into an IVF-ICSI programme. When an andrological patient has plasma FSH values >10 IU/l and/or very low total motile sperm count <1 x 10(6), despite a normal karyotype, they clearly need a testicular biopsy and a meiotic study in order to rule out meiotic arrest or synaptic anomalies. Another important aspect to be considered is the possible benefit of applying preimplantation genetic diagnosis in these cases because they normally have a high percentage of chromosomally abnormal embryos, although in the present study this was not evident. All studies agree on the necessity of conducting follow-up studies in the population of children born after IVF-ICSI. In this way, it will be possible to find out if these infertile patients and their offspring have a higher risk of suffering epigenetic errors and imprinting disorders.

Gonadotrophin-releasing hormone-antagonists vs long agonist in in-vitro fertilization patients with polycystic ovary syndrome: a meta-analysis

Aim. This article is a systematic review of the literature to establish whether there is an advantage in the use of GnRH antagonists (Ant) compared to the long agonist protocol (Ago) in patients with polycystic ovarian syndrome (PCOS). Material and methods. The meta-analysis was conducted using the MIX software with Mantel–Haenszel weighting method and the fixed effect model. Results. Five studies were identified. We analyzed 269 Ant and 303 Ago cycles. Pregnancy rates and the incidence of ovarian hyperstimulation syndrome (OHSS) were analyzed in all five studies, abortion rates were analyzed on three. Pregnancy rates did not differ between the groups: 137/269 (Ant Group) versus 172/303 (Ago Group) (OR: 0.80 CI: [0.57–1.11]). The incidence of OHSS per Ant (13/269) was significantly lower compared to the Ago (35/303) (OR: 0.47 CI: [0.24–0.92]). No difference was found between the two groups in the abortion rate: 10/77 (Ant Group) versus 9/88 (Ago Group) (OR: 1.29 CI: [0.49–3.36]). Conclusion. The limited evidence present in literature suggests that in patients with PCOS there is no difference between a long Ago and an Ant protocol in terms of pregnancy and abortion rates. It seems more likely that the use of the Ant may reduce the incidence of OHSS.

Heterotopic pregnancy in a cross border oocyte donation patient: the importance of cooperation between centers

OBJECTIVE To report a case of tubal heterotopic pregnancy after oocyte donation in a cross border patient. DESIGN Case report. SETTING Private University Clinic, Spain, and Public University Hospital, Italy. PATIENT(S) A woman with a tubal heterotopic pregnancy after oocyte donation. INTERVENTION(S) Oocyte donation and ET (Spain), laparoscopic removal of the tubal heterotopic pregnancy (Italy). MAIN OUTCOME MEASURE(S) Diagnosis and treatment of the heterotopic pregnancy. RESULT(S) Laparoscopic treatment of the heterotopic pregnancy resulting in a single ongoing intrauterine pregnancy. CONCLUSION(S) Cross border reproductive care is increasing in Europe. When patients go back to their respective countries of origin they may not inform their doctors about having undergone fertility treatments abroad. This can lead to a delayed diagnosis in case of complications arising after treatment or during pregnancy. It is of vital importance that clinicians are aware of this possibility to speed up the diagnosis and treatment of potentially fatal situations such as the one described in the present case report.

Should progesterone on the human chorionic gonadotropin day still be measured

OBJECTIVE To evaluate in our setting whether there is currently a level of P on the hCG day (P-hCG) predictive of no pregnancy. DESIGN Observational study of prospectively collected data of the P-hCG levels of stimulated IVF cycles. SETTING In vitro fertilization unit. PATIENT(S) All cycles of IVF/intracytoplasmic sperm injection with fresh embryo transfer performed between January 2009 and March 2014. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Pregnancy rate. RESULT(S) Clinical pregnancy rate per ET was 38.7% and live birth rate was 29.1%. The P-hCG concentration was positively correlated to E2 on the hCG day, and the number of oocytes was negatively correlated to age. Progesterone on hCG day was higher among agonist- compared with antagonist-treated patients (mean ± SD: 1.13 ± 0.69 ng/mL vs. 0.97 ± 0.50 ng/mL) and among recombinant FSH compared with recombinant FSH + hMG stimulation (mean ± SD: 1.11 ± 0.58 ng/mL vs. 0.94 ± 0.50 ng/mL). Pregnancy rate was positively associated with the number of oocytes. There was no correlation between P-hCG value and pregnancy rate, overall or according to the type of treatment. CONCLUSION(S) In our setting there is no P-hCG value differentiating a good from a poor cycle success rate. CLINICAL TRIAL REGISTRATION NUMBER NCT02323347.

Poor prognosis for ovarian response to stimulation: results of a randomised trial comparing the flare-up GnRH agonist protocol vs. the antagonist protocol.

Objective. To determine the efficacy of the flare-up agonist and the antagonist protocols in patients with poor prognosis for ovarian response. Methods. A randomised trial was conducted on two hundred and twenty-one women considered as having poor prognosis for ovarian response to stimulation, based on previous cycles or clinical criteria. All women were prospectively randomised into two groups of treatment (flare-up group and antagonist group) by computer-assisted randomisation in a 1:1 ratio. The main outcome measure was clinical pregnancy rate. Results. Groups were homogeneous in age and baseline characteristics. Duration of stimulation, gonadotropin consumption, number of oocytes retrieved and number and quality of embryos transferred did not differ significantly between the groups. E2 level the day of hCG administration was significantly higher in the flare-up group. Pregnancy rates per started cycle were 15% in the flare-up group and 14.1% in the antagonist group. Cancellation rates were 12.5% in the flare-up group and 16.3% in the antagonist group. None of these differences reached statistical significance. Conclusions. No statistically significant differences were observed between the two protocols regarding clinical pregnancy rates. In patients with poor prognosis for ovarian response, the flare-up agonist and the antagonist protocols were comparable regarding clinical pregnancy rates.

Replacing GnRH agonists with GnRH antagonists in oocyte recipient cycle did not adversely affect the pregnancy rates

UNLABELLED The synchronization of the donor stimulation with the endometrial preparation of the recipient is usually done by downregulating the recipients pituitary with a GnRH analog. OBJECTIVE The aim of this study is to compare pregnancy and implantation rates among premenopausal oocyte recipients synchronized by pituitary suppression with GnRH agonist (Group AGO) or antagonist (Group ANTAG) and standard endometrial preparation with estrogen and gestagen. STUDY DESIGN Prospective, observational, transversal, comparative study. Consecutive recipients treated at Institut Universitari Dexeus between July 2008 and December 2009. RESULTS One hundred and eighty-three premenopausal women were included. No differences were found regarding the age of donors nor the age of recipients, fertilization rates, number of embryos transferred and embryo quality. No differences were found in clinical pregnancy rates (56.1% Group AGO vs. 52.4% Group ANTAG). CONCLUSION The administration of GnRH antagonists during endometrial preparation in oocyte recipients facilitates synchronization without affecting the pregnancy rate.