Modified natural cycle allows a window of 7 days for frozen embryo transfer planning.

RESEARCH QUESTION: Should ovulation be triggered in a modified natural cycle (mNC) with recombinant human chorionic gonadotrophin (rHCG) as soon as a mean follicle diameter of 17 mm is visible, or is more flexible planning possible? DESIGN: This multicentre, retrospective, observational study of 3087 single frozen blastocyst transfers in mNC was carried out between January 2020 and September 2022. The inclusion criteria included endometrial thickness ≥7 mm and serum progesterone <1.5 ng/ml. The main outcome was ongoing pregnancy rate. Secondary end-points were pregnancy rate, implantation rate, clinical pregnancy rate and miscarriage rate. The mean follicle size at triggering was stratified into three groups (13.0-15.9, 16.0-18.9 and 19.0-22 mm). RESULTS: The baseline characteristics between the groups did not vary significantly for age, body mass index and the donor's age for egg donation. No differences were found in pregnancy rate (64.5%, 60.2% and 57.4%; P = 0.19), clinical pregnancy rate (60.5%, 52.8% and 50.6%; P = 0.10), implantation rate (62.10%, 52.9% and 51.0%; P = 0.05) or miscarriage rate (15.0%, 22.2%; and 25.0%; P = 0.11). Although ongoing pregnancy rate (54.9%, 46.8% and 43.1%; P = 0.02) varied significantly in the univariable analysis, it was no longer significant after adjustment for the use of preimplantation genetic testing for aneuploidies and egg donation. CONCLUSIONS: The findings showed rHCG could be flexibly administered with a mean follicle size between 13 and 22 mm as long as adequate endometrial characteristics are met, and serum progesterone is <1.5 ng/ml. Considering the follicular growth rate of 1-1.5 mm/day, this approach could allow a flexibility for FET scheduling of 6-7 days, simplifying mNC FET planning in clinical practice.

Natural proliferative phase frozen embryo transfer-a new approach which may facilitate scheduling without hindering pregnancy outcomes.

STUDY QUESTION: How does a natural proliferative phase (NPP) strategy for frozen embryo transfer (FET) compare with the conventional artificial (AC) and natural (NC) endometrial preparation protocols in terms of live birth rates (LBR)? SUMMARY ANSWER: This study supports the hypothesis that, just as for NC, NPP-FET may be a superior alternative to AC in terms of LBR. WHAT IS KNOWN ALREADY: Although FETs are increasing worldwide, the optimal FET protocol is still largely controversial. Despite recent evidence supporting a possibly higher efficacy and safety of NC FETs, their widespread use is limited by the difficulties encountered during cycle monitoring and scheduling. STUDY DESIGN, SIZE, DURATION: In this single center retrospective cohort study, we describe the NPP-FET protocol, in which vaginal progesterone is initiated during the proliferative phase as soon as an endometrium with a thickness of at least 7 mm is identified and ovulation is ruled out, regardless of mean diameter of the dominant follicle. PARTICIPANTS/MATERIALS, SETTING, METHODS: For comparison, we considered all blastocyst stage FET cycles preformed at a private infertility center between January 2010 and June 2022, subdivided according to the following subgroups of endometrial preparation: AC, NPP, and NC. We performed multivariable generalized estimating equations regression analysis to account for the following potential confounding variables: oocyte age at retrieval, oocyte source (autologous without preimplantation genetic testing for aneuploidies (PGT-A) versus autologous with PGT-A versus donated), number of oocytes retrieved/donated, embryo developmental stage (Day 5 versus Day 6), number of embryos transferred, quality of the best embryo transferred, and year of treatment. The main outcome measure was LBR. The secondary outcomes included hCG positive, clinical pregnancy and miscarriage rates, and the following perinatal outcomes: first trimester bleeding, second/third trimester bleeding, preterm rupture of membranes, gestational diabetes, gestational hypertensive disorders (GHD), and gestational age at delivery. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 5791 FET cycles were included in this analysis (2226 AC, 349 NPP, and 3216 NC). The LBR for FET was lower in the AC subgroup when compared to the NPP and NC (38.4%, 49.1%, and 45.2%, respectively; P < 0.01 AC versus NPP and AC versus NC). The rates of miscarriage were also lower in the NPP and NC subgroups when compared to AC (19.7%, 25.0%, and 34.9%, respectively; P < 0.01 NPP versus AC and NC versus AC). Considering perinatal outcomes, NPP-FET and NC were associated with a significantly lower first trimester bleeding compared to AC (17.3%, 14.7%, and 37.6%, respectively; P < 0.01 NPP versus AC and NC versus AC). Additionally, NC was associated with a lower rate of GHD when compared with AC (8.6% versus 14.5%, P < 0.01), while the rate following NPP-FET was 9.4%. LIMITATIONS, REASONS FOR CAUTION: This study is limited by its retrospective design. Moreover, there was also a low number of patients in the NPP subgroup, which may have led the study to be underpowered to detect clinically relevant differences between the subgroups. WIDER IMPLICATIONS OF THE FINDINGS: Our study posits that the NPP-FET protocol may be an effective and safe alternative to both NC and AC, while still allowing for enhanced practicality in patient follow-up and FET scheduling. Further investigation on NPP-FET is warranted, with prospective studies including a larger and more homogeneous subsets of patients. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the IVI-RMA-Lisbon (2008-LIS-053-CG). The authors did not receive any funding for this study. The authors have no competing interests. TRIAL REGISTRATION NUMBER: Not applicable.

Screening for diminished ovarian reserve in Portugal: a cost-saving answer to shorten the fertility journey.

Aim: Assess the budget impact of nationwide screening for diminished ovarian reserve (OR), via anti-Müllerian hormone (AMH) levels, to the Portugal National Health System (NHS). Patients & methods: The clinical journey was determined using literature and the family planning decision-making process/response using survey results. A panel of four local clinicians validated all assumptions/inputs. Results: Screening for OR led to an expected savings of € 9.4 million for the NHS, driven by a 24% reduction in medically assisted reproduction (MAR) use. When needed, referral for MAR was earlier and more women used first-line versus second-line techniques. The model estimated a 12% decrease in failure. Conclusion: This model shows AMH screening may allow more informed decisions, leading to a shorter fertility journey, more efficient use of treatments, and substantial cost-savings for the NHS.

The combined effect of BMI and age on ART outcomes.

STUDY QUESTION: For a woman with infertility and overweight/obesity, can infertility treatment be postponed to first promote weight loss? SUMMARY ANSWER: Advice regarding a delay in IVF treatment to optimize female weight should consider female age, particularly in women over 38 years for whom only substantial weight loss in a short period of time (3 months) seems to provide any benefit. WHAT IS KNOWN ALREADY: Body weight excess and advanced age are both common findings in infertile patients, creating the dilemma of whether to promote weight loss first or proceed to fertility treatment immediately. Despite their known impact on fertility, studies assessing the combined effect of female age and BMI on cumulative live birth rates (CLBRs) are still scarce and conflicting. STUDY DESIGN, SIZE, DURATION: We performed a multicentre retrospective cohort study including 14 213 patients undergoing their first IVF/ICSI cycle with autologous oocytes and subsequent embryo transfers, between January 2013 and February 2018 in 18 centres of a multinational private fertility clinic. BMI was subdivided into the following subgroups: underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), and obesity (≥30.0 kg/m2). PARTICIPANTS/MATERIALS, SETTING, METHODS: The primary outcome was CLBR. The secondary outcome was time to pregnancy. To assess the influence of female age and BMI on CLBR, two multivariable regression models were developed with BMI being added in the models as either an ordinal categorical variable (Model 1) or a continuous variable (Model 2) using the best-fitting fractional polynomials. CLBR was estimated over 1-year periods (Model 1) and shorter timeframes of 3 months (Model 2). We then compared the predicted CLBRs according to BMI and age. MAIN RESULTS AND THE ROLE OF CHANCE: When compared to normal weight, CLBRs were lower in women who were overweight (adjusted odds ratio (aOR) 0.86, 95% CI 0.77-0.96) and obese (aOR 0.74, 95% CI 0.62-0.87). A reduction of BMI within 1 year, from obesity to overweight or overweight to normal weight would be potentially beneficial up to 35 years old, while only a substantial reduction (i.e. from obesity to normal BMI) would be potentially beneficial in women aged 36-38 years. Above 38 years of age, even considerable weight loss did not compensate for the effect of age over a 1-year span but may be beneficial in shorter time frames. In a timeframe of 3 months, there is a potential benefit in CLBR if there is a loss of 1 kg/m2 in BMI for women up to 33.25 years and 2 kg/m2 in women aged 33.50-35.50 years. Older women would require more challenging weight loss to achieve clinical benefit, specifically 3 kg/m2 in women aged 35.75-37.25 years old, 4 kg/m2 in women aged 37.50-39.00 years old, and 5 kg/m2 or more in women over 39.25 years old. LIMITATIONS, REASONS FOR CAUTION: This study is limited by its retrospective design and lower number of women in the extreme BMI categories. The actual effect of individual weight loss on patient outcomes was also not evaluated, as this was a retrospective interpatient comparison to estimate the combined effect of weight loss and ageing in a fixed period on CLBR. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that there is potential benefit in weight loss strategies within 1 year prior to ART, particularly in women under 35 years with BMI ≥25 kg/m2. For those over 35 years of age, weight loss should be considerable or occur in a shorter timeframe to avoid the negative effect of advancing female age on CLBR. A tailored approach for weight loss, according to age, might be the best course of action. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was obtained for this study. All authors have no conflicts to declare. TRIAL REGISTRATION NUMBER: N/A.

Perinatal outcomes in children born after fresh or frozen embryo transfer using donated oocytes.

STUDY QUESTION: Do children born after vitrified-thawed embryo transfers (ETs) using donated oocytes have worse perinatal outcomes when compared with fresh ET? SUMMARY ANSWER: No significant difference in birthweight and prematurity rates between fresh or frozen embryo transfers (FETs) in newborns after oocyte donation was found. WHAT IS KNOWN ALREADY: Autologous singletons born after fresh ET have been previously associated with higher rates of preterm birth and low birthweight, while FETs seem to confer a higher risk of hypertensive disorders during pregnancy and macrosomia. However, studies comparing these outcomes using autologous oocytes are unable to adequately disentangle the putative detrimental consequences of embryo vitrification from the possible effects that ovarian stimulation and endometrial preparation may have on endometrial receptivity prior to ET. The oocyte donation model is, for this reason, a more appropriate setting to study these hypotheses; however so far, the information available regarding neonatal outcomes in this patient population is limited to either small and/or heterogeneous studies. STUDY DESIGN, SIZE, DURATION: We performed a multicentre retrospective cohort study including 5848 singletons born between 2009 and February 2020 following oocyte donation and single blastocyst transfer, subdivided according to whether a fresh ET or FET was performed. We also performed two additional sensitivity analyses, subgrouping the sample according to the type of endometrial preparation (natural versus artificial) and whether the donated oocytes had previously been vitrified or not. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients with a first singleton livebirth after single blastocyst transfer were compared using multivariable regression analysis to account for potential confounding factors. The primary outcome was birthweight. Secondary outcomes were birthweight z-scores and percentiles, small/large for gestational age, gestational age at delivery, gender, prematurity (<37 weeks and <32 weeks), neonatal morbidity (Apgar scores and need for neonatal intensive care) and maternal morbidity (gestational hypertensive disorders, gestational diabetes and caesarean delivery). MAIN RESULTS AND THE ROLE OF CHANCE: There was no significant difference between the fresh ET and FET groups in terms of mean birthweight (3215 g versus 3200 g) and birthweight z-scores (0.03 versus 0.1), in both the unadjusted and confounder-adjusted models. However, artificial endometrial preparation was associated with a higher birthweight (3220 g versus 3105 g) and birthweight z-scores (0.06 versus -0.13) when compared with a transfer in a natural cycle. Although a 1-day statistically significant difference in gestational age at birth (275 versus 274 days) was detected, premature birth rates (<37 weeks) did not vary significantly between groups (9.9% and 11.2% for fresh ET and FET, respectively). No other statistically significant differences were found in the remaining neonatal and maternal outcomes studies between the fresh ET and FET groups. LIMITATIONS, REASONS FOR CAUTION: This study is limited by its retrospective design and lack of information regarding congenital malformations. Moreover, the sample selection criteria that were used may limit the generalizability of our results. WIDER IMPLICATIONS OF THE FINDINGS: Perinatal outcomes did not seem to be affected significantly by the embryo vitrification process in an oocyte donation model. Hence, other factors may contribute to the hindered perinatal outcomes described in ART, particularly the potential effect that ovarian stimulation and endometrial preparation may have on endometrial receptivity. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was obtained for this study. All authors have no conflicts to declare. TRIAL REGISTRATION NUMBER: N/A.

Donor IUI is equally effective for heterosexual couples, single women and lesbians, but autologous IUI does worse.

STUDY QUESTION: Are there differences in the clinical outcomes of IUI among different populational groups (heterosexual couples, single women and lesbian couples)? SUMMARY ANSWER: The outcome of donor IUI (D-IUI) is similar in all populational groups and better than that seen with autologous insemination. WHAT IS KNOWN ALREADY: A vast body of literature on clinical outcome is available for counselling heterosexual couples regarding decisions related to ART. The reproductive potential of single women, lesbian couples and heterosexual couples who need donor semen is assumed to be better, but there is a scarcity of data on their ART performance to actually confirm it. STUDY DESIGN, SIZE, DURATION: In this retrospective multicentric cohort study, a total of 7228 IUI treatment cycles performed in 3807 patients between January 2013 and December 2016 in 13 private clinics belonging to the same reproductive medicine group in Spain were included. Patients with previous IUI attempts were excluded from the study. Only 1.9% of cycles were lost to follow-up. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 5318 D-IUI cycles were performed in three different populational groups: heterosexual couples (D-HC, 1167 cycles), single women (SW, 2839 cycles) and lesbian couples (LC, 1312), while a total of 1910 autologous IUI cycles were performed in heterosexual couples (A-HC). This last one was considered the control group and was composed of cycles performed in couples with a male partner with sperm parameters equivalent to those requested from donors. In order to identify factors with an impact on clinical outcome, a multivariate logistic regression analysis was performed. Regarding live birth rate (LBR), mixed effect models were employed to control for the fact that different patients were submitted to different numbers of treatments. MAIN RESULTS AND THE ROLE OF CHANCE: Parameters that were significant to the primary outcome (LBR) according to the multivariate analysis were the populational group (D-HC, SW, LC and A-HC) to which the patient belonged, female age and a diagnosis of low ovarian reserve. At the age range of good prognosis (≤37 years), LBR was similar in all groups that underwent D-IUI (18.8% for D-HC, 16.5% for SW and 17.6% for LC) but was significantly lower in the autologous IUI (A-HC) group (11%). For all these significant findings, the strength of the association was confirmed by P values <0.001. From 38 years of age on, no significant differences were observed among the populational groups studied, and for all of them, LBR was below 7% from 40 years of age on. LIMITATIONS, REASONS FOR CAUTION: To the best of our knowledge, a smoking habit was the only known factor with a potential effect on ART outcome that could not be controlled for, due to the unavailability of this information in a significant percentage of the clinical files studied. Our study was not capable of precisely quantifying the impact of a diagnosis of low ovarian reserve on the LBR of both IUI and D-IUI, due to the number of cycles performed in patients with such diagnosis (n = 231, 3.2% of the total). WIDER IMPLICATIONS OF THE FINDINGS: For the first time, a comparison among D-HC, SW, LC and A-HC was performed in a study with a robust sample size and controlling for potential sources of bias. There is now sound evidence that equivalent clinical outcome is seen in the three groups treated with donor semen (D-HC, SW and LC). Specifically, regarding the comparison between SW and LC, our findings rule out differences in LBR proposed by previous publications, with very similar clinical outcomes within the same age ranges. At age ranges of good prognosis (≤37 years), reproductive performance of D-IUI is significantly better than that seen in heterosexual couples undergoing autologous IUI, even when only cases of optimal sperm quality are considered in this last group. This finding is in agreement with the concept that, as a group, A-HC are more prone to have female factor infertility, even when their infertility assessment finds no contraindication to IUI. Age affects all these groups equally, with none of them reaching a 7% LBR after the age of 40 years. Our findings will be useful for the counselling of patients from the different populations studied here about ART strategies. STUDY FUNDING/COMPETING INTEREST(S): None.

Ovarian stimulation under the effect of isotretinoin.

Isotretinoin (13-cis-retinoic acid) is a pharmaceutical vitamin A analog that is frequently used in the treatment of severe cystic acne, many women at reproductive age being exposed to this substance. This drug has a clearly documented teratogenicity and data from rodents and humans indicate that a direct aggression to ovarian follicles also occurs. Here we report the case of a 29-year-old woman with breast cancer referred for emergency preservation of reproductive potential that used isotretinoin up to the day before the initiation of ovarian stimulation. Ultrasound scan showed an antral follicle count of 17 and 13 follicles on the right and the left ovary, respectively, and her antimüllerian hormone levels were 4.03 ng/ml. Standard ovarian stimulation for oocyte vitrification in oncological patients was initiated during the luteal phase and final estradiol levels were 49 pg/ml. Three mature oocytes were obtained. Other four oocytes were retrieved in the germinal vesicle and metaphase I developmental stage, all of which matured in vitro in the following 30 h and were also vitrified. Response to ovarian stimulation, both in terms of the number of mature oocytes obtained and serum sex steroids production were in the lower range of what is observed in patients with a similar clinical profile. These findings suggest that isotretinoin impairs follicular-oocyte maturation.

Lights and Shadows about the Effectiveness of IVF in HIV Infected Women: A Systematic Review.

BACKGROUND: HIV infected women have higher rates of infertility. Objective. The purpose of this literature review is to evaluate the effectiveness of fresh IVF/ICSI cycles in HIV infected women. MATERIALS AND METHODS: A search of the PubMed database was performed to identify studies assessing fresh nondonor oocyte IVF/ICSI cycle outcomes of serodiscordant couples with an HIV infected female partner. RESULTS AND DISCUSSION: Ten studies met the inclusion criteria. Whenever a comparison with a control group was available, with the exception of one case, ovarian stimulation cancelation rate was higher and pregnancy rate (PR) was lower in HIV infected women. However, statistically significant differences in both rates were only seen in one and two studies, respectively. A number of noncontrolled sources of bias for IVF outcome were identified. This fact, added to the small size of samples studied and heterogeneity in study design and methodology, still hampers the performance of a meta-analysis on the issue. Conclusion. Prospective matched case-control studies are necessary for the understanding of the specific effects of HIV infection on ovarian response and ART outcome.

Pharmacologic therapies in endometriosis: a systematic review.

To assess the literature on preclinical and clinical efficacy and safety data of pharmacologic groups proposed in the treatment of endometriosis, we performed a systematic review of publications from March 2002 to January 2012 via PubMed search. Additional relevant articles were identified from citations within these publications. A high number of medications were tested in preclinical models of endometriosis due to their theoretic capacity of disrupting important pathophysiologic pathways of the disease, such as inflammatory response, angiogenesis and cell survival, proliferation, migration, adhesion, and invasion. Tumor necrosis factor α-blockers, nuclear factor κB inhibitors, antiangiogenic agents, statins, antioxidants, immunomodulators, flavonoids, histone deacetylase inhibitors, matrix metalloproteinase inhibitors, metformin, novel modulators of sex steroids expression, and apoptotic agents were all effective in in vitro/animal models. Most of these agents have not been tried in the clinical setting, mainly because of the high risk of adverse effects. However, some of them can be used in humans. Dopamine agonists and valproic acid have already been tested in pilot studies with good results. Etanercept, metformin, and statins are used in humans for other indications, and endostatin is now being tested in phase 2 oncologic trials. These drugs may constitute alternatives to conventional therapy with estrogen inhibitors and anti-inflammatory agents.

Etiology of OHSS and use of dopamine agonists.

Vascular endothelial growth factor is the factor that causes increased capillary permeability and therefore the most serious manifestations of ovarian hyperstimulation syndrome. Dopamine agonists can both prevent and treat ovarian hyperstimulation syndrome by blocking expression of the vascular endothelial growth factor receptor.

Targeting the vascular endothelial growth factor system to prevent ovarian hyperstimulation syndrome.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) typically occurs when ovaries are primed with FSH/LH and subsequently exposed to hCG. The ultimate pathophysiological step underlying this clinical picture is increased vascular permeability (VP). METHODS: A search of the literature was carried out using PubMed and the authors' files. RESULTS: In rodents and humans, the expression of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2) mRNA increases during ovarian stimulation. With the administration of hCG, the expression of each rises to a maximum. Expression of VEGF/VEGFR-2 mRNAs correlates with enhanced VP, with both peaking 48 h following an injection of hCG. Immunohistochemistry shows the presence of VEGF and VEGFR-2 proteins in the granulosa-lutein and endothelial cells of the entire corpus luteum. Increased VP may be mediated through adhesion molecules such as VE-cadherin, which is involved in the loosening of endothelial intercellular junctions. These findings regarding the pathophysiology of OHSS suggest that the syndrome can be prevented by inducing ovulation with LH or GnRH analogues, which prevent VEGF overexpression. Also, co-administration of a dopamine agonist inhibits phosphorylation of the receptor VEGFR-2. In a trial of 69 oocyte donors, the incidence of moderate OHSS was 20% with the dopamine agonist cabergoline and 44% with a placebo (P = 0.04). CONCLUSIONS: The pathophysiological mechanisms involved in OHSS suggest potential preventive approaches, but larger trials are necessary for evaluating the efficacy and safety of the pharmaco-prevention of OHSS.

Clinical factors affecting endometrial receptiveness in oocyte donation cycles.

OBJECTIVE: To provide a summary of the actual knowledge about the clinical factors affecting the oocyte recipient (other than those associated with uterine cavity abnormalities) on the outcome of oocyte donation cycles. DESIGN: Review of the literature. SETTING: Information regarding the association between age, body mass index (BMI), endometrial priming, tobacco consumption, hydrosalpinx, and endometriosis/adenomyosis in oocyte recipients and the results of oocyte donation cycles. RESULT(S): Recipient age and the presence of hydrosalpinx are clearly associated with a poorer outcome in oocyte donation cycles. The negative impact of tobacco consumption has recently been confirmed. The exact relevance of an elevated BMI is under debate but it is likely that it determines a lower ongoing pregnancy rate (PR). Endometriosis may be significant for endometrial receptiveness in the context of a natural cycle, but no negative impact is detected when standard endometrial priming protocols are used in oocyte donation. The same may be true for adenomyosis, although its relevance to endometrial receptiveness is less clear. CONCLUSION(S): Accumulated knowledge in the field of oocyte donation has led to the recognition of clinical variables that affect cycle outcome by impairing endometrial receptiveness. Many studies are being carried out on endometrial molecular and gene expression changes taking place in these circumstances. In the near future a comprehensive understanding of these processes should be achieved, from a genetic, molecular, and clinical perspective. These advances in the collective knowledge will lead to an improvement in the diagnosis and treatment of infertile patients.

Air bubble location inside the uterus after transfer: is the embryo really there?

OBJECTIVE: To demonstrate that the location of the air bubble after embryo transfer (ET) does not necessarily indicate the final embryo location. DESIGN: Case report. SETTING: Private clinic. PATIENT(S): A couple with primary infertility for whom a diagnosis of bicornuate uterus with a very open angle between horns was confirmed. INTERVENTION(S): Laparoscopy and hysteroscopy were performed before an IVF cycle in which a single embryo was replaced. MAIN OUTCOME MEASURE(S): Air bubble image immediately after ET and gestational sac location 3 weeks later. RESULT(S): Immediately after a single ET, the air bubble was seen in the left uterine horn. Three weeks later, a gestational sac was seen in the right uterine horn. CONCLUSION(S): The location of the air bubble immediately after ET does not necessarily indicate the final embryo location.

Improvements achieved in an oocyte donation program over a 10-year period: sequential increase in implantation and pregnancy rates and decrease in high-order multiple pregnancies.

OBJECTIVE: To compare outcome parameters and cumulative pregnancy rates (PRs) in oocyte donation cycles over a period of 10 years. DESIGN: Retrospective study. SETTING: University-affiliated assisted reproductive technology program. PATIENT(S): Women undergoing oocyte donation (10,537 cycles) between 1995 and 2005. INTERVENTION(S): Ovarian stimulation and oocyte retrieval in donors. Embryo transfer performed in recipients after endometrial preparation. MAIN OUTCOME MEASURE(S): Outcome parameters and cumulative PRs were calculated and compared in relation to indication, age, and origin of sperm used. RESULT(S): Overall PR, implantation rate, clinical PR, and miscarriage rate per embryo transfer performed were 54.9%, 27%, 50.3%, and 19%, respectively. Ongoing PR per transfer was 40.2%, and twin and high-order multiple PRs were 39% and 6%, respectively. Mean number of embryos transferred was reduced from 3.6 +/- 0.8 to 1.9 +/- 0.3, implantation rate improved from 16.7% to 38.3%, and ongoing PR improved from 31% to 44.3%. Cumulative PRs did not differ significantly among different indications for oocyte donation, age groups, or origin of sperm used for oocyte insemination. Overall cumulative PRs after three and five cycles were calculated as 87% and 96.8%, respectively. CONCLUSION(S): Significant improvements in outcome parameters were achieved within 10 years. Similar cumulative PRs were observed regardless of recipient age, indication for oocyte donation, or sperm origin.

Age and uterine receptiveness: predicting the outcome of oocyte donation cycles.

CONTEXT: The impact of advancing age on uterine receptiveness has always been a concern of the medical establishment. Oocyte donation (OD) is the perfect model for ascertaining the extent of this relationship, but the literature is somewhat unreliable, mainly due to the limited samples on which the studies are based and insufficient control of important variables such as embryo quality. SETTING: The present work was developed in a private infertility clinic. PATIENTS OR OTHER PARTICIPANTS: We retrospectively evaluate the results of 3089 OD cycles that ended up in a d 3 embryo transfer. Severe male factor infertility was an exclusion criterion. MAIN OUTCOME MEASURES: The impact of patients' age on pregnancy, implantation, and miscarriage rates and obstetric outcome is analyzed, as is the relevance of endometrial thickness, serum estradiol levels, and duration of exogenous estrogen therapy to said rates. RESULTS: Pregnancy and implantation rates are significantly reduced and miscarriage rate is significantly increased from 45 yr of age onward. Concerning obstetric outcome, incidences of hypertension, proteinuria, premature rupture of membranes, second- and third-trimester hemorrhage, and preterm delivery are higher and mean birth weight is lower in this age group. With regard to endometrial preparation, estrogen therapy lasting more than 7 wk is associated with reduced PR and IR (P = 0.01 and P = 0.02, respectively). CONCLUSIONS: The results of OD cycles and obstetric outcome are significantly worse when recipients are 45 yr of age or older. Concerning endometrial preparation, results are significantly worse when estrogen therapy lasts more than 7 wk.

Intravenous albumin does not prevent moderate-severe ovarian hyperstimulation syndrome in high-risk IVF patients: a randomized controlled study.

BACKGROUND: Intravenous albumin administration has been described for many years as a debatable, but probably useful preventive measure in ovarian hyperstimulation syndrome (OHSS). The present study details the largest randomized controlled trial to date of albumin infusion versus no treatment in IVF patients with a high risk of developing moderate to severe OHSS. METHODS: Between March 1999 and February 2002, women undergoing IVF at the IVI Valencia with >20 retrieved oocytes were included. A total of 988 patients was initially enrolled. Immediately after oocyte retrieval, patients were allocated to two groups based on a computer randomization: the first group received 40 g human albumin; the second group received no treatment. Subjects were weighed and a blood analysis performed immediately after oocyte retrieval and again 7 days later. Women were monitored on an outpatient basis until menstruation, or until fetal heart activity was detected. Twelve subjects were excluded due to follow-up loss, leaving 976 women (377 of them oocyte donors), with 488 in each group. RESULTS: No difference was found between the two groups in terms of patient characteristics and outcome. Moderate-severe and severe-only OHSS rates were similar. The incidence of haemoconcentration and liver and renal dysfunction at 7 days after oocyte retrieval was similar in the two groups. In women who developed moderate/severe (n = 66) or only severe (n = 46) OHSS, there was no difference based on prior albumin administration between blood parameters or body weight on the day of oocyte retrieval, 7 days later, and even when comparing variation between both measurements. Moreover, the number of patients with paracentesis, hospital admissions, complications and days of OHSS until resolution did not differ. CONCLUSIONS: Albumin infusion on the day of oocyte retrieval is not a useful means of preventing the development of moderate-severe OHSS.

Avaliaçäo da cavidade uterina pela histerossonografia / Hysterossonography in the evaluation of the uterine cavity

OBJETIVO: Avaliar a acurácia da histerossonografia na detecçäo de patologias uterinas intracavitárias, comparando os resultados com o ultra-som transvaginal convencional, com a histerossalpingografia e com a histeroscopia. MATERIAL E MÉTODOS: Foram avaliadas 36 mulheres com suspeita de patologia uterina intracavitária empregando-se a histerossonografia, ultra-sonografia transvaginal e histeroscopia. Dessas pacientes, 22 foram avaliadas também pela histerossalpingografia. A histerossonografia foi realizada com a distensäo da cavidade uterina por meio da infusäo de soluçäo salina, utilizando a sonda ZUI-2.0. Os achados da histeroscopia para a cavidade uterina foram considerados padräo ouro. Os métodos foram comparados pela sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo, tendo sido utilizado ainda o índice de Kappa para avaliar o grau de concordância dos exames com a histeroscopia. RESULTADOS: A histerossonografia foi superior (sensibilidade 90,9 por cento, especificidade 92,3 por cento) à histerossalpingografia (sensibilidade 64,3 por cento, especificidade 75,0 por cento) na detecçäo de patologias uterinas intracavitárias, sendo ainda mais eficiente que a ultra-sonografia transvaginal convencional (sensibilidade 72,7 por cento, especificidade 84,6 por cento). O valor preditivo positivo para a histerossonografia foi de 95,2 por cento e o valor preditivo negativo de 85,7 por cento, enquanto o valor preditivo positivo para a histerossalpingografia foi de 81,8 por cento e o valor preditivo negativo de 54,6 por cento. O valor preditivo positivo e o valor preditivo negativo para a ultra-sonografia foram respectivamente de 88,9 por cento e 64,7 por cento. O índice de Kappa encontrou a melhor concordância (77 por cento) entre a histerossonografia e a histeroscopia, ficando as demais em 62,5 por cento (ultra-sonografia e histeroscopia) e 48,8 por cento (histerossalpingografia e histeroscopia). CONCLUSÄO: A histerossonografia representa uma melhora importante em relaçäo ao ultra-som convencional na detecçäo de patologias uterinas intracavitárias, sendo ainda muito superior à histerossalpingografia para este fim, devendo, portanto, substitui-la na propedêutica da cavidade uterina.

A eletroejaculaçäo como técnica de reproduçäo assistida / Electroejaculation as a assisted reproductive technique

A incapacidade ejaculatória responde por menos de 3 por cento dos casos de infertilidade por fator masculino. Para estes pacientes, no entanto, representa a incapacidade de gerar filhos. Os fatores causais desse quadro säo: lesäo da medula espinhal, dissecçäo de linfonodos retroperitoneais, diabete melito, mielite transversa, esclerose múltipla ou desordens psicogênicas. A eletroejaculaçäo surge como uma alternativa para esses pacientes: induz-se ejaculaçäo com uma sonda transretal, através de estímulo elétrico à musculatura lisa e fibras nervosas autonômicas simpáticas da regiäo da ampola da uretra pélvica e vesículas seminais. O preparo dos pacientes inclui: alcalinizaçäo da urina e lavagem vesical, já que a maior parte da ejaculaçäo é retrógrada, uma vez que a eletroejaculaçäo näo coordena o fechamento do colo vesical, e antibioticoprofilaxia. O paciente é colocado em posiçäo de litotomia ou decubito lateral esquerdo. Uma vez introduzida a sonda, controla-se a voltagem, corrente elétrica, duraçäo do estímulo elétrico e temperatura da mucosa retal. A maior parte dos pacientes apresenta uma pequena quantidade de ejaculado anterógrado gotejante e a fraçäo mais importante do mesmo é retrógrada, sendo recuperada da bexiga através de sondagem vesical. O sêmen é entäo beneficiado e utilizado para inseminaçäo intra-uterina. As complicaçöes, raras, em espasmo transitório das extremidades e lesäo do reto. A disreflexia autonômica, um grave quadro, praticamente inexiste, utilizando-se previamente a nifedipina nos pacientes de risco. A eletroejaculaçäo tem obtido ejaculado em aproximadamente 90 por cento dos casos, com concentraçäo em torno de 180 a 300 milhöes de espermatozóides por ejaculado e motilidade ruim, em torno de 22 por cento. Em nosso serviço, já realizamos procedimentos de eletroejaculaçäo em quatro pacientes (15 séries de estímulo elétrico), com obtençäo de sêmen com motilidade semelhante ao descrito na literatura e sem registro de alguma complicaçäo.