Progestogens for prevention of luteinising hormone (LH) surge in women undergoing controlled ovarian hyperstimulation as part of an assisted reproductive technology (ART) cycle.

BACKGROUND: Currently, gonadotrophin releasing hormone (GnRH) analogues are used to prevent premature ovulation in ART cycles. However, their costs remain high, the route of administration is invasive and has some adverse effects. Oral progestogens could be cheaper and effective to prevent a premature LH surge. OBJECTIVES: To evaluate the effectiveness and safety of using progestogens to avoid spontaneous ovulation in women undergoing controlled ovarian hyperstimulation (COH). SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group trials register, CENTRAL, MEDLINE, Embase and PsycINFO in Dec 2021. We contacted study authors and experts to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that included progestogens for ovulation inhibition in women undergoing controlled ovarian hyperstimulation (COH). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane, including the risk of bias (RoB) assessment. The primary review outcomes were live birth rate (LBR) and oocyte pick-up cancellation rate (OPCR). Secondary outcomes were clinical pregnancy rate (CPR), cumulative pregnancy, miscarriage rate (MR), multiple pregnancies, LH surge, total and MII oocytes, days of stimulation, dose of gonadotropins, and moderate/severe ovarian hyperstimulation syndrome (OHSS) rate. The primary analyses were restricted to studies at overall low and some concerns RoB, and sensitivity analysis included all studies. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included 14 RCTs (2643 subfertile women undergoing ART, 47 women used oocyte freezing for fertility preservation and 534 oocyte donors). Progestogens versus GnRH antagonists We are very uncertain of the effect of medroxyprogesterone acetate (MPA) 10 mg compared with cetrorelix on the LBR in poor responders (odds ratio (OR) 1.25, 95% confidence interval (CI) 0.73 to 2.13, one RCT, N = 340, very-low-certainty evidence), suggesting that if the chance of live birth following GnRH antagonists is assumed to be 18%, the chance following MPA would be 14% to 32%. There may be little or no difference in OPCR between progestogens and GnRH antagonists, but due to wide Cs (CIs), we are uncertain (OR 0.92, 95%CI 0.42 to 2.01, 3 RCTs, N = 648, I² = 0%, low-certainty evidence), changing the chance of OPCR from 4% with progestogens to 2% to 8%. Given the imprecision found, no conclusions can be retrieved on CPR and MR. Low-quality evidence suggested that using micronised progesterone in normo-responders may increase by 2 to 6 the MII oocytes in comparison to GnRH antagonists. There may be little or no differences in gonadotropin doses. Progestogens versus GnRH agonists Results were uncertain for all outcomes comparing progestogens with GnRH agonists. One progestogen versus another progestogen The analyses comparing one progestogen versus another progestogen for LBR did not meet our criteria for primary analyses. The OPCR was probably lower in the MPA 10 mg in comparison to MPA 4 mg (OR 2.27, 95%CI 0.90 to 5.74, one RCT, N = 300, moderate-certainty evidence), and MPA 4 mg may be lower than micronised progesterone 100 mg, but due to wide CI, we are uncertain of the effect (OR 0.81, 95%CI 0.43 to 1.53, one RCT, N = 300, low-certainty evidence), changing the chance of OPCR from 5% with MPA 4 mg to 5% to22%, and from 17% with micronised progesterone 100 mg to 8% to 24%. When comparing dydrogesterone 20 mg to MPA, the OPCR is probably lower in the dydrogesterone group in comparison to MPA 10 mg (OR 1.49, 95%CI 0.80 to 2.80, one RCT, N = 520, moderate-certainty evidence), and it may be lower in dydrogesterone group in comparison to MPA 4 mg but due to wide confidence interval, we are uncertain of the effect (OR 1.19, 95%CI 0.61 to 2.34, one RCT, N = 300, low-certainty evidence), changing the chance of OPCR from 7% with dydrogesterone 20 to 6-17%, and in MPA 4 mg from 12% to 8% to 24%. When comparing dydrogesterone 20 mg to micronised progesterone 100 mg, the OPCR is probably lower in the dydrogesterone group (OR 1.54, 95%CI 0.94 to 2.52, two RCTs, N=550, I² = 0%, moderate-certainty evidence), changing OPCR from 11% with dydrogesterone to 10% to 24%. We are very uncertain of the effect in normo-responders of micronised progesterone 100 mg compared with micronised progesterone 200 mg on the OPCR (OR 0.35, 95%CI 0.09 to 1.37, one RCT, N = 150, very-low-certainty evidence). There is probably little or no difference in CPR and MR between MPA 10 mg and dydrogesterone 20 mg. There may be little or no differences in MII oocytes and gonadotropins doses. No cases of moderate/severe OHSS were reported in most of the groups in any of the comparisons. AUTHORS' CONCLUSIONS: Little or no differences in LBR may exist when comparing MPA 4 mg with GnRH agonists in normo-responders. OPCR may be slightly increased in the MPA 4 mg group, but MPA 4 mg reduces the doses of gonadotropins in comparison to GnRH agonists. Little or no differences in OPCR may exist between progestogens and GnRH antagonists in normo-responders and donors. However, micronised progesterone could improve by 2 to 6 MII oocytes. When comparing one progestogen to another, dydrogesterone suggested slightly lower OPCR than MPA and micronised progesterone, and MPA suggested slightly lower OPCR than the micronised progesterone 100 mg. Finally, MPA 10 mg suggests a lower OPCR than MPA 4 mg. There is uncertainty regarding the rest of the outcomes due to imprecision and no solid conclusions can be drawn.

How effective are the non-conventional ovarian stimulation protocols in ART? A systematic review and meta-analysis.

PURPOSE: To compare the effectiveness of starting the ovarian stimulation on the early follicular phase ("Conventional") with the newer range of non-conventional approaches starting in the luteal phase ("Luteal"), random-start, and studies implementing them in DuoStim ("Conventional"+"Luteal"). METHODS: Systematic review. We searched CENTRAL, PubMed, and Embase, on March 2020. We included randomized and non-randomized controlled trials that compared "Luteal," random-start ovarian stimulation or DuoStim with "Conventional"; we analyzed them by subgroups: oocyte freezing and patients undergoing ART treatments, both, in the general infertile population and among poor responders. RESULTS: The following results come from a sensitivity analysis that included only the low/moderate risk of bias studies. When comparing "Luteal" to "Conventional," clinically relevant differences in MII oocytes were ruled out in all subgroups. We found that "Luteal" probably increases the COH length both, in the general infertile population (OR 2.00 days, 95% CI 0.81 to 3.19, moderate-quality evidence) and in oocyte freezing cycles (MD 0.85 days, 95% CI 0.53 to 1.18, moderate-quality evidence). When analyzing DuoStim among poor responders, we found that it appears to generate a higher number of MII oocytes in comparison with a single "Conventional" (MD 3.35, 95%CI 2.54-4.15, moderate-quality evidence). CONCLUSION: Overall, this systematic review of the available data demonstrates that in poor responders, general infertile population and oocyte freezing for cancer stimulation in the late follicular and luteal phases can be utilized in non-conventional approaches such as random-start and DuoStim cycles, offering similar outcomes to the conventional cycles but potentially with increased flexibility, within a reduced time frame. However, more well-designed trials are required to establish certainty.

Endometrial preparation for women undergoing embryo transfer with frozen embryos or embryos derived from donor oocytes.

BACKGROUND: A frozen embryo transfer (FET) cycle is when one or more embryos (frozen during a previous treatment cycle) are thawed and transferred to the uterus. Some women undergo fresh embryo transfer (ET) cycles with embryos derived from donated oocytes. In both situations, the endometrium is primed with oestrogen and progestogen in different doses and routes of administration. OBJECTIVES: To evaluate the most effective endometrial preparation for women undergoing transfer with frozen embryos or embryos from donor oocytes with regard to the subsequent live birth rate (LBR). SEARCH METHODS: The Cochrane Gynaecology and Fertility Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, LILACS, trials registers and abstracts of reproductive societies' meetings were searched in June 2020 together with reference checking and contact with study authors and experts in the field to identify additional studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating endometrial preparation in women undergoing fresh donor cycles and frozen embryo transfers. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. We analysed all available interventions versus placebo, no treatment, or between each other. The primary review outcome was live birth rate. Secondary outcomes were clinical and multiple pregnancy, miscarriage, cycle cancellation, endometrial thickness and adverse effects. MAIN RESULTS: Thirty-one RCTs (5426 women) were included. Evidence was moderate to very low-quality: the main limitations were serious risk of bias due to poor reporting of methods, and serious imprecision. Stimulated versus programmed cycle We are uncertain whether a letrozole-stimulated cycle compared to a programmed cycle, for endometrial preparation, improves LBR (odds ratio (OR) 1.26, 95% confidence interval (CI) 0.49 to 3.26; 100 participants; one study; very low-quality evidence). Stimulating with follicle stimulating hormone (FSH), letrozole or clomiphene citrate may improve clinical pregnancy rate (CPR) (OR 1.63, 95% CI 1.12 to 2.38; 656 participants; five studies; I2 = 11%; low-quality evidence). We are uncertain if they reduce miscarriage rate (MR) (OR 0.79, 95% CI 0.36 to 1.71; 355 participants; three studies; I2 = 0%; very low-quality evidence). Endometrial thickness (ET) may be reduced with clomiphene citrate (mean difference(MD) -1.04, 95% CI -1.59 to -0.49; 92 participants; one study; low-quality evidence). Other outcomes were not reported. Natural versus programmed cycle We are uncertain of the effect from a natural versus programmed cycle for LBR (OR 0.97, 95% CI 0.74 to 1.28; 1285 participants; four studies; I2 = 0%; very low-quality evidence) and CPR (OR 0.79, 95% CI 0.62 to 1.01; 1249 participants; five studies; I2 = 60%; very low-quality evidence), while a natural cycle probably reduces the cycle cancellation rate (CCR) (OR 0.60, 95% CI 0.44 to 0.82; 734 participants; one study; moderate-quality evidence). We are uncertain of the effect on MR and ET. No study reported other outcomes. Transdermal versus oral oestrogens From low-quality evidence we are uncertain of the effect transdermal compared to oral oestrogens has on CPR (OR 0.86, 95% CI 0.59 to 1.25; 504 participants; three studies; I2 = 58%) or MR (OR 0.55, 95% CI 0.27 to 1.09; 414 participants; two studies; I2 = 0%). Other outcomes were not reported. Day of starting administration of progestogen When doing a fresh ET using donated oocytes in a synchronised cycle starting progestogen on the day of oocyte pick-up (OPU) or the day after OPU, in comparison with recipients that start progestogen the day prior to OPU, probably increases the CPR (OR 1.87, 95% CI 1.13 to 3.08; 282 participants; one study, moderate-quality evidence). We are uncertain of the effect on multiple pregnancy rate (MPR) or MR. It probably reduces the CCR (OR 0.28, 95% CI 0.11 to 0.74; 282 participants; one study; moderate-quality evidence). No study reported other outcomes. Gonadotropin-releasing hormone (GnRH) agonist versus control A cycle with GnRH agonist compared to without may improve LBR (OR 2.62, 95% CI 1.19 to 5.78; 234 participants; one study; low-quality evidence). From low-quality evidence we are uncertain of the effect on CPR (OR 1.08, 95% CI 0.82 to 1.43; 1289 participants; eight studies; I2 = 20%), MR (OR 0.85, 95% CI 0.36 to 2.00; 828 participants; four studies; I2 = 0%), CCR (OR 0.49, 95% CI 0.21 to 1.17; 530 participants; two studies; I2 = 0%) and ET (MD -0.08, 95% CI -0.33 to 0.16; 697 participants; four studies; I2 = 4%). No study reported other outcomes. Among different GnRH agonists From very low-quality evidence we are uncertain if cycles among different GnRH agonists improves CPR or MR. No study reported other outcomes. GnRH agonists versus GnRH antagonists GnRH antagonists compared to agonists probably improves CPR (OR 0.62, 95% CI 0.42 to 0.90; 473 participants; one study; moderate-quality evidence). We are uncertain of the effect on MR and MPR. No study reported other outcomes. Aspirin versus control From very low-quality evidence we are uncertain whether a cycle with aspirin versus without improves LBR, CPR, or ET. Steroids versus control From very low-quality evidence we are uncertain whether a cycle with steroids compared to without improves LBR, CPR or MR. No study reported other outcomes. AUTHORS' CONCLUSIONS: There is insufficient evidence on the use of any particular intervention for endometrial preparation in women undergoing fresh donor cycles and frozen embryo transfers. In frozen embryo transfers, low-quality evidence showed that clinical pregnancy rates may be improved in a stimulated cycle compared to a programmed one, and we are uncertain of the effect when comparing a programmed cycle to a natural cycle. Cycle cancellation rates are probably reduced in a natural cycle. Although administering a GnRH agonist, compared to without, may improve live birth rates, clinical pregnancy rates will probably be improved in a GnRH antagonist cycle over an agonist cycle. In fresh synchronised oocyte donor cycles, the clinical pregnancy rate is probably improved and cycle cancellation rates are probably reduced when starting progestogen the day of or day after donor oocyte retrieval. Adequately powered studies are needed to evaluate each treatment more accurately.

Quality of evidence matters: is it well reported and interpreted in infertility journals?

PURPOSE: To evaluate if the authors of published systematic reviews (SRs) reported the level of quality of evidence (QoE) in the top 5 impact factor infertility journals and to analyze if they used an appropriate wording to describe it. METHODS: This is a cross-sectional study. We searched in PubMed for SRs published in 2017 in the five infertility journals with the highest impact factor. We analyzed the proportion of SRs published in the top 5 impact factor infertility journals that reported the SRs' QoE, and the proportion of those SRs in which authors used consistent wording to describe QoE and magnitude of effect. RESULTS: The QoE was reported in only 21.4% of the 42 included SRs and in less than 10% of the abstracts. Although we did not find important differences in the report of QoE of those that showed statistically significant differences or not, p value was associated with the wording chosen by the authors. We found inconsistent reporting of the size the effect estimate in 54.8% (23/42) and in the level of QoE in 92.9% (39/42). Whereas the effect size was more consistently expressed in studies with statistically significant findings, QoE was better expressed in those cases in which the p value was over 0.05. CONCLUSION: We found that in 2017, less than 25% of the authors reported the overall QoE when publishing SRs. Authors focused more on statistical significance as a binary concept than on methodological limitations like study design, imprecision, indirectness, inconsistency, and publication bias. Authors should make efforts to report the QoE and interpret results accordingly.

Physicians and patients' motivations to perform elective single or double-embryo transfers: A nationwide survey.

OBJECTIVES: To evaluate motivations to perform an elective single embryo transfer (e-SET). METHODS: Cross-sectional surveys to reproductive medicine specialists and to infertile patients undergoing assisted reproductive treatments. RESULTS: In the physician's survey (n = 278), we found that the main reasons for not offering e-SET were the physicians' belief that patients prefer optimizing the pregnancy rates regardless of the potential complications (57.1%). Regarding the decision making process, 76.7% of physicians thought that patients and doctors should make these decisions together and 93.3% would like to have a more formal decision-aid to help with counseling. In the patients' survey (n = 100), 21.3% chose e-SET, while 33% mentioned that complications associated to multiple pregnancies were insufficiently discussed. Among those patients, none chose to have e-SET, while 30% of those who had a full discussion selected e-SET (p = 0.05). CONCLUSIONS: Most physicians did not offer e-SET based on potential patients' negative feelings. Also, almost 30% take important decisions without the patient's participation. Patients that discussed more thoroughly this topic, more frequently selected e-SET. Almost all the physicians surveyed agreed that decision-aids could help in this important shared-decision process. PRACTICE IMPLICATIONS: Decision aids about e-SET vs DET are needed to help patients in the decision making process.

[Successful treatment of a cervical heterotopic pregnancy following an in vitro fertilization procedure]. / Tratamiento exitoso de un embarazo heterotópico cervical luego de un procedimiento de fecundación in vitro.

A 37-year-old nulligravida infertile female had a cervical heterotopic pregnancy following an in vitro fertilization procedure. Early intervention on the 6th week of gestation with a manual vacuum aspirator reached to remove the cervical pregnancy. Ligation of the descending cervical branches of the uterine arteries and a cervical cerclage, were placed before the aspiration, for prevention of possible hemorrhage. Successful removal of the cervical pregnancy was achieved with only mild bleeding. An intrauterine pregnancy progressed to viability without complications, resulting in a vaginal delivery of a preterm live-birth at 35.4 weeks, of a male that weighted 2740 g.

Tratamiento exitoso de un embarazo heterotópico cervical luego de un procedimiento de fecundación in vitro / Successful treatment of a cervical heterotopic pregnancy following an in vitro fertilization procedure

Mujer nulípara infértil de 37 años presentó un embarazo heterotópico cervical luego de tratamiento por fecundación in vitro. Una intervención temprana durante la 6ta semana de gestación logró remover el saco cervical mediante un aspirador manual. Para prevenir una posible hemorragia, se realizó la ligadura de las ramas cérvico-uterinas y se colocó un cerclaje cervical, antes de la aspiración. Se logró extraer el embarazo cervical con mínima hemorragia. El embarazo intrauterino progresó sin complicaciones, resultando en el parto de un varón de 2740 g, a las 35.4 semanas.

A 37-year-old nulligravida infertile female had a cervical heterotopic pregnancy following an in vitro fertilization procedure. Early intervention on the 6th week of gestation with a manual vacuum aspirator reached to remove the cervical pregnancy. Ligation of the descending cervical branches of the uterine arteries and a cervical cerclage, were placed before the aspiration, for prevention of possible hemorrhage. Successful removal of the cervical pregnancy was achieved with only mild bleeding. An intrauterine pregnancy progressed to viability without complications, resulting in a vaginal delivery of a preterm live-birth at 35.4 weeks, of a male that weighted 2740 g.

Misleading reporting and interpretation of results in major infertility journals.

OBJECTIVE: To evaluate the proportion of randomized controlled trials (RCTs) published in top infertility journals indexed on PubMed that reported their results with proper effect estimates and their precision estimation, while correctly interpreting both measures. DESIGN: Cross-sectional study evaluating all the RCTs published in top infertility journals during 2014. SETTING: Not applicable. PATIENT(S): Not applicable. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Proportion of RCTs that reported both relative and absolute effect size measures and its precision. RESULT(S): Among the 32 RCTs published in 2014 in the top infertility journals reviewed, 37.5% (95% confidence interval [CI], 21.1-56.3) did not mention in their abstracts whether the difference among the study arms was statistically or clinically significant, and only 6.3% (95% CI, 0.8-20.8) used a CI of the absolute difference. Similarly, in the results section, these elements were observed in 28.2% (95% CI, 13.7-46.7) and 15.6% (95% CI, 5.3-32.8), respectively. Only one study clearly expressed the minimal clinically important difference in their methods section, but we found related proxies in 53% (95% CI, 34.7-70.9). None of the studies used CIs to draw conclusions about the clinical or statistical significance. We found 13 studies where the interpretation of the findings could be misleading. CONCLUSION(S): Recommended reporting items are underused in top infertility journals, which could lead to misleading interpretations. Authors, reviewers, and editorial boards should emphasize their use to improve reporting quality.

Quality of reporting in infertility journals.

OBJECTIVE: To evaluate whether fertility and top gynecology journals indexed in PubMed require the use of reporting guidelines and to identify the percentage of randomized controlled trials (RCTs) published in 2013 that were written following CONSORT guidelines in the top four fertility journals (by their highest impact factor). DESIGN: Cross-sectional study evaluating instructions for authors and RCTs published in fertility journals. SETTING: Academic institution. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Proportion of instruction-for-authors documents that suggested or required the use of reporting guidelines, and proportion of RCTs published in 2013 that accomplished the CONSORT checklist. RESULT(S): In 47% (16/34) of the journals one or more reporting guidelines were mentioned in the instructions for authors' documents. PRISMA and CONSORT were the most commonly mentioned reporting guidelines. None of the analyzed RCTs completed the 25 items of CONSORT guideline. Sequence generation or allocation concealment was not described in 69% of the studies. One-third of the journals did not publish a flowchart, 72% did not show relative and absolute size-effect measures, and 42% did not use measures of imprecision. In the summaries, 42% did not discuss the limitations of the study and 78% did not mention the generalizability of the results. CONCLUSION(S): Less than half of the analyzed peer-reviewed journals request the authors to use reporting guidelines. Nevertheless, among the top fertility and gynecology journals, reporting guidelines are widely mentioned. Overall, accomplishment of CONSORT items was suboptimal. Editorial boards, reviewers, and authors should join efforts to improve the quality of reporting.

Vitrification versus slow freezing for women undergoing oocyte cryopreservation.

BACKGROUND: Oocyte cryopreservation is a technique with considerable potential in reproductive medicine, including  fertility preservation, as a way of delaying childbearing and as part of oocyte donation programs. Although the technique was relatively ineffective at first more recently numerous modifications have led to higher success rates. OBJECTIVES: To compare the effectiveness and safety of vitrification and slow freezing as oocyte cryopreservation techniques for fertility outcomes in women undergoing assisted reproduction. SEARCH METHODS: We searched electronic databases, trial registers and websites, including the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and PsycINFO (date of search 3 March 2014). SELECTION CRITERIA: Two review authors independently selected randomised controlled trials (RCTs) comparing vitrification and slow freezing for oocyte preservation in women undergoing assisted reproduction. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data from eligible studies and assessed their risk of bias. Any disagreements were resolved by discussion or by a third review author. Data extracted included study characteristics and outcome data. The overall quality of the evidence was assessed using GRADE methods. MAIN RESULTS: Two RCTs were included in the review (106 participants). Neither study reported live birth rate. Vitrification was associated with an increased clinical pregnancy rate compared to slow freezing (RR 3.86, 95% CI 1.63 to 9.11, P = 0.002, 2 RCTs, 106 women, I(2) = 8%, moderate quality evidence). The effect of vitrification compared to slow freezing on ongoing pregnancy rates was only reported in one small study, with inconclusive findings (RR 6.07, 95% CI 0.86 to 43.04, P = 0.07, one RCT, 28 women, low quality evidence).No data were reported on adverse effects, nor were any other outcomes reported in the included trials. The evidence was limited by imprecision. We assessed the included studies as at low to unclear risk of bias as the methods were not well described. AUTHORS' CONCLUSIONS: Oocyte vitrification compared to slow freezing probably increases clinical pregnancy rates in women undergoing assisted reproduction. However, the total number of women and pregnancies were low and the imprecision is high which limits applicability. The effect on ongoing pregnancy is uncertain as data were sparse. No data were available on live births or adverse effects.

Changes in DNA fragmentation during sperm preparation for intracytoplasmic sperm injection over time.

OBJECTIVE: To compare the DNA fragmentation of semen samples established by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) after incubation in polyvinylpyrrolidone (PVP) and hyaluronic acid (HA) for different time periods. DESIGN: Comparative prospective study. SETTING: Center for reproductive medicine. PATIENT(S): Twenty-seven semen samples from infertile patients. INTERVENTION(S): None. METHODS: Semen analysis and DNA fragmentation assays (TUNEL) were performed. Two groups were established: A) normal TUNEL (<20%); and B) Abnormal TUNEL (≥ 20%). TUNEL was performed in neat (T0), postgradient (TG), 1-hour postgradient (TG1), and 2-hour postgradient (TG2) samples and in TG2 samples after 0.5, 1.0, and 1.5 hours of incubation in PVP or HA. RESULT(S): TUNEL levels were significantly reduced after gradient separation compared with neat values. In group A, TUNEL levels were significantly higher in the TG2 + 1.5 hours in PVP and HA samples but did not reach abnormal levels. In group B, TUNEL levels were significantly higher in the TG2 + 1 hour in PVP and HA samples. CONCLUSION(S): Sperm DNA fragmentation significantly decreased after centrifugation gradient, regardless of the initial levels of the sample. Samples with TUNEL ≥ 20% were more susceptible to a significant increase in DNA fragmentation over time, with similar increases being observed over time for samples that were incubated in HA or PVP. These data may be relevant for sperm preparation for intracytoplasmic sperm injection.

A shared egg donor program: which is the minimum number of oocytes to be allocated?

PURPOSE: To evaluate which is the minimum number of oocytes to be allocated to each recipient in a shared egg donor program. METHODS: We analyzed 953 recipients that received at least 4 metaphase II (MII) oocytes in the period 2006-2008. We retrospectively divided the recipients according to the number of MII oocytes actually received. RESULTS: No statistically significant differences were found among the analyzed strata in clinical pregnancy rate (A:43.7%; B:45.6%; C:48.6%; D:45.5%; E:53%, P=NS) and miscarriage rate. However, the rate of top quality transferred embryos, and the embryo freezing rate were significantly higher among those recipients that received 7 or more mature eggs. CONCLUSIONS: After a large sample was analyzed, no significant differences in fresh embryo transfer outcome were encountered when a different number of oocytes was allocated. A minimum of 4 MII oocytes seems to achieve satisfactory pregnancy rates in our shared egg donor program.

Effect of vascular endothelial growth factor and interleukin-1beta on apoptosis in endometrial cell cultures from patients with endometriosis and controls.

The aim of this study was to evaluate the effect of vascular endothelial growth factor (VEGF) and interleukin-1beta (IL-1beta) on apoptosis induced by leuprolide acetate (LA) in endometrial epithelial cell cultures from patients with endometriosis. Primary endometrial epithelial cell cultures were obtained from uterine endometrial biopsies of patients with endometriosis and control women. Endometrial epithelial cells were incubated with LA; a combination of LA and VEGF; a combination of LA and IL-1beta; or in basal conditions. LA was added 3h prior to addition of VEGF and IL-1beta. After stimulation, the percentage of apoptotic cells was evaluated by the acridine orange-ethidium bromide technique and Bax expression was assessed by western blot. Treatment with LA enhanced the percentage of apoptotic cells in endometrial epithelial cells from subjects with endometriosis and control subjects. Addition of either VEGF or IL-1beta after exposure to LA restored the percentage of apoptotic cells to basal levels. Moreover, treatment with LA increased Bax expression in endometrial epithelial cells from patients with endometriosis. This effect was reverted by the addition of either VEGF or IL-1beta. Our results show that VEGF and IL-1beta reduce apoptosis and decrease Bax expression in endometrial epithelial cells from patients with endometriosis. This study suggests that VEGF and IL-1beta may protect endometriotic cells from undergoing apoptosis in addition to exerting their pro-angiogenic role.

Endometrial preparation for women undergoing embryo transfer with frozen embryos or embryos derived from donor oocytes.

BACKGROUND: If a fresh embryo, assisted reproductive technology procedure cycle is unsuccessful and there are frozen embryos available, a frozen-thawed embryo transfer is performed. In some specific cases women may undergo oocyte donation treatment. In both situations the endometrium is primed by the administration of estrogen and progesterone. To prevent the possibility of spontaneous ovulation, gonadotropin-releasing hormone (GnRH) agonists are frequently used. OBJECTIVES: To evaluate the most effective endometrial preparation for women undergoing transfer with frozen embryos or embryos from donor oocytes with regard to the subsequent live birth rate. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, LILACS, and abstracts of reproductive societies' meetings (from inception). No language restrictions were applied. Experts in the field were contacted. SELECTION CRITERIA: Randomised controlled trials evaluating endometrial preparation in women undergoing fresh donor cycles and frozen embryo transfers. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the inclusion criteria, assessed trial risk of bias, and extracted data. MAIN RESULTS: Twenty two randomised controlled trials were included. Five studies analysed the use of a GnRH agonist versus control. No significant benefit was demonstrated when using GnRH agonists. No evidence of statistically significant benefit was found for one GnRH agonist over another, or vaginal over intramuscular progesterone administration. No difference in pregnancy rate was demonstrated when no treatment was compared to aspirin, steroids, ovarian stimulation, or human chorionic gonadotropin (hCG) prior to embryo transfer, although using hCG several times before the oocyte retrieval decreases the pregnancy rate. Finally, when oocyte recipients were studied further, starting progesterone on the day of oocyte pick-up (OPU) or the day after OPU produced a significantly higher pregnancy rate (OR 1.87, 95% CI 1.13 to 3.08) than when recipients started progesterone the day prior to OPU. AUTHORS' CONCLUSIONS: There is insufficient evidence to recommend any one particular protocol for endometrial preparation over another with regard to pregnancy rates after embryo transfers. These were either frozen embryos or embryos derived from donor oocytes. However, there is evidence of a lower pregnancy rate and a higher cycle cancellation rate when the progesterone supplementation is commenced prior to oocyte retrieval in oocyte donation cycles. Adequately powered studies are needed to evaluate each treatment more accurately.

Effect of aromatase inhibitors on ectopic endometrial growth and peritoneal environment in a mouse model of endometriosis.

OBJECTIVE: To evaluate the effect of aromatase inhibitors on ectopic endometrial growth and on the release of proangiogenic and proinflammatory factors in peritoneal fluid (PF). DESIGN: Prospective experimental study. SETTING: Animal research and laboratory facility. ANIMAL(S): Female Balb/c mice 2 months of age. INTERVENTION(S): Mice had surgery performed to induce endometriosis-like lesions. Treatment with anastrozole or letrozole was started on either postoperative day 1 or 28 and continued for 4 weeks. MAIN OUTCOME MEASURE(S): Endometriotic lesions were counted and measured and aromatase expression, cell proliferation, and apoptosis were assessed. Vascular endothelial growth factor (VEGF) and prostaglandin E (PGE) levels were evaluated in the PF. RESULT(S): Endometriosis-like lesions express aromatase P-450. Treatment with either anastrozole or letrozole did not prevent lesion establishment; however, it significantly decreased the size of the endometriotic lesion. When treatment was initiated on postoperative day 1, letrozole and anastrozole decreased cell proliferation and increased apoptosis. When treatment was started on postoperative day 28, both aromatase inhibitors decreased cell proliferation, but only anastrozole augmented apoptosis levels. In addition, letrozole reduced VEGF and PGE levels in PF. Anastrozole diminished VEGF content but did not cause any significant change in PGE levels. CONCLUSION(S): These findings support the further investigation of aromatase inhibition as a treatment option for endometriosis.

64-Row multidetector CT virtual hysterosalpingography.

OBJECTIVE: To illustrate the large variety of pathologies found on 64-row computed tomographic (CT) virtual hysterosalpingography (CT-VHSG) in the evaluation of the female reproductive tract in infertile patients. MATERIAL AND METHODS: We prospectively evaluated CT datasets from 209 patients with diagnosis of infertility. CT-VHSG was performed with a 64-row CT scanner using 64 x 0.625 mm(2) collimation and 0.9 mm slice thickness. A total volume of 20 mL of an iodine contrast dilution was injected into the uterine cavity. The duration of the CT scan and the grade of patient discomfort of the procedure were documented. Images were analyzed on a workstation. The CT-VHSG exams were divided in studies with normal or pathological findings; pathologies were classified according to their locations (cervical, uterine, and fallopian tube pathology). RESULTS: No complications occurred during the procedure. The mean scan time was 3.4 +/- 0.4 s; the mean patient effective dose was 2.58 +/- 0.75 mSv. In relation to the patient's discomfort evaluation, 55.5% of the patients referred no discomfort during the procedure. Cervical pathology was found in 100/209 patients, uterine pathology in 93/209 patients, and fallopian tubes pathology in 37/209 patients. CONCLUSION: A 64-row CT-VHSG provides a reliable, non-invasive alternative diagnostic technique in the infertility workup algorithm.

Clinical use of 64-row multislice computed tomography hysterosalpingography in the evaluation of female factor infertility.

OBJECTIVE: To evaluate the potential clinical value of 64-row multislice computed tomography hysterosalpingography (MSCT-H) in the evaluation of female patients with a diagnosis of infertility and compare it with the use of standard X-ray hysterosalpingography (HSG). DESIGN: Comparative prospective study. SETTING: Outpatient Imaging Diagnostic Centre, Diagnóstico Maipú, Buenos Aires, Argentina, and a university-affiliated fertility institute (Centro de Estudios en Ginecología y Reproducción, Buenos Aires, Argentina). PATIENT(S): Twenty-two female patients with a diagnosis of infertility. INTERVENTION(S): Sixty-four-row MSCT-H and conventional X-ray HSG. MAIN OUTCOME MEASURE(S): Diagnostic accuracy of MSCT-H for the evaluation of cervical, uterine, and tubal pathology. RESULT(S): We found that 64-row MSCT-H was useful in identifying female reproductive tract abnormalities, showing in the per patient analysis a sensitivity of 100% and a specificity of 85.71%. This new procedure can be performed without a tenaculum, making it well tolerated. Clinical complications did not occur in any of the patients participating in the study. CONCLUSION(S): Sixty-four-row MSCT-H is a valuable alternative diagnostic technique in the infertility workup algorithm for the evaluation of the female reproductive tract.

Virtual hysteroscopy by multidetector computed tomography.

Currently accepted techniques that evaluate the uterus and female reproductive system in the infertility workup algorithm include hysterosonography, hysteroscopy and hysterosalpingography. Based on high speed multidetector computed tomography (MDCT) which can acquire high-quality volumetric data of the pelvic region in a single brief scan, MDCT virtual hysteroscopy is proposed as a developing, non-invasive alternative diagnostic procedure for the evaluation of uterine pathology and other gynecologic disorders. Findings of the technique are illustrated.

Multidetector computed tomography virtual hysterosalpingography in the investigation of the uterus and fallopian tubes.

OBJECTIVE: To compare the efficacy of multidetector CT virtual hysterosalpingography (MDCT-VH) with conventional X-ray hysterosalpingography (HSG) in the evaluation of patients with diagnosis of infertility. METHODS: Sixty patients with diagnosis of infertility scheduled to perform a HSG, were evaluated with 16-row (n=50) and 64-row (n=10) MDCT-VH. In 35 patients the examination was performed without a tenaculum. The HSGs were carried out using standard technique. The HSG and MDCT-VH findings were compared. The duration for both examinations and patient discomfort were documented. The sensitivity and specificity of MDCT-VH for the detection of uterine pathology and tubal obstruction were calculated using the exact binomial method. Agreement between the two methods was assessed by the Cohen's kappa method (k). RESULTS: The mean duration for MDCT-VH (16 and 64-rows) was 5+/-3 min, whereas for HSG was 28+/-3. The MDCT-VH without a tenaculum was the procedure with less patient discomfort. Sensitivity, specificity and inter-method agreement for the detection of uterine pathology were 100%, 92% and k=0.92 for 16-row MDCT-VH and 100%, 100% and k=1 for 64-row MDCT-VH, respectively. Sensitivity and specificity for detection of tubal obstruction were 80% and 80% for 16-row MDCT-VH and 100% and 100% for 64-row MDCT-VH, respectively; inter-method agreement for the visualization of the tubes was k=0.54 for 16-row MDCT-VH and k=1 for 64-row MDCT-VH. CONCLUSION: This study demonstrated the feasibility of evaluating the female reproductive system by MDCT-VH. 64-Row MDCT-VH could be an alternative diagnostic technique in the infertility workup algorithm. A larger study is in progress to validate these encouraging results.

Significance of ovarian macrophages in the follicular aspirates from ART patients.

PURPOSE: To evaluate the percentages of macrophages present in granulosa cells (GC) cultures from patients with different responses to the hyperstimulation, in relation to the percentages of apoptotic cells (ApC), as well as to the release of cytokines. METHODS: We studied 42 patients: 12 Hyporesponders, (with < or =4 follicles), 15 Normoresponders, (5-14 follicles), and 15 Hyperresponders, (> or =15 follicles). In GC cultures percentages of macrophages and ApC were counted and, in the conditioned media, cytokines were measured. RESULTS: Percentages of macrophages were significantly higher in GC cultures from Hyporesponders compared with Hyperresponders patients. Also, the percentages of ApC cells were the highest in Hyporesponders. On the contrary, cytokines concentrations were the lowest in this group. CONCLUSIONS: The low ovarian response is probably due to the decreased angiogenesis, which in turn produces increased apoptosis and decreased production of cytokines. The increased percentage of macrophages could be related to increased frequency of apoptotic cells.