Hyperstimulation Cycles Research Articles

Treatment of Unexplained Infertility by Acupuncture in Natural and Control Ovarian Hyperstimulation Cycles: A Prospective Analysis

Acupuncture is an important method of treatment in Chinese medicine. The objective of this study was to evaluate the efficacy of acupuncture as an adjuvant treatment for unexplained infertility. Here we conducted a prospective study, with data consisting of acupuncture group (38 cases) and control group (42 cases). Infertility evaluation workup consisted of semen analysis, ovulation assessment, hysterosalpingogram (HSG) and blood analysis. The patients in acupuncture group received 3 acupuncture sessions, and each at seven acupuncture points (EX-CA1, CV4, CV6, SP10, ST36, SP6, and KI3). The session started 12 days before menstruation and continued for 10 days. The patients in control group did not receive acupuncture. All patients tried 1 - 3 natural cycles 3 months after HSG test, if not pregnant, underwent 1 - 3 cycles of control ovarian hyperstimulation (COH) and timed intercourse. Pregnancy was evaluated by measurement of blood β human chorionic gonadotrophin (β-hCG) and subsequent trans-vaginal ultrasound. No significant difference of clinical pregnancy rate was found between the acupuncture group and the control group, however, numbers of COH cycles were significantly less and more pregnancies occurred in natural cycle in the acupuncture group. We concluded that acupuncture can be used as an adjuvant treatment for unexplained infertility. Although acupuncture did not increase the cumulative pregnancy rate, it decreased the number of COH cycles and more patients got pregnant in natural cycles after receiving acupuncture.

Differences in cumulus cells gene expression between modified natural and stimulated in vitro fertilization cycles

The aim of our study was to determine whether there are any differences in the cumulus cell gene expression profile of mature oocytes derived from modified natural IVF and controlled ovarian hyperstimulation cycles and if these changes could help us understand why modified natural IVF has lower success rates. Cumulus cells surrounding mature oocytes that developed to morulae or blastocysts on day 5 after oocyte retrieval were submitted to microarray analysis. The obtained data were then validated using quantitative real-time PCR. There were 66 differentially expressed genes between cumulus cells of modified natural IVF and controlled ovarian hyperstimulation cycles. Gene ontology analysis revealed the oxidation-reduction process, glutathione metabolic process, xenobiotic metabolic process and gene expression were significantly enriched biological processes in MNIVF cycles. Among differentially expressed genes we observed a large group of small nucleolar RNA's whose role in folliculogenesis has not yet been established. The increased expression of genes involved in the oxidation-reduction process probably points to hypoxic conditions in modified natural IVF cycles. This finding opens up new perspectives for the establishment of the potential role that oxidation-reduction processes have in determining success rates of modified natural IVF.

Cetrorelix in COH cycles: time of change for the daily administered dose? A response to Kerimoğlu et al. (10.1007/s00404-013-2806-z)

It is with great interest that we have read the paper published in your journal by Kerimoglu et al. [1] which addresses an important clinical question: the decrease of daily administered Cetrorelix dose in controlled ovarian hyperstimulation (COH) cycles to avoid premature LH surge while improving pregnancy rates mainly by the subsequent modifications at a cellular level. However, the article reports somewhat precipitate ‘conclusions’, which have the potential for misinterpretation and are in contrast, in several ways, with some important studies published in the past (see Table 1). Firstly, a ‘dose-finding’ study cannot be, by definition, ‘‘retrospective’’. Therefore, it is premature to state that ‘there is no difference...’ between the two regimens, as there have been studies in the past (even referred in Kerimoglu’s et al. [1]), with a prospective and, sometimes, even with a randomized design that clearly state that the lowest daily effective dosage for pituitary down-regulation with Cetrorelix is 0.25 mg/day. Furthermore, in an important—because of its design— randomized controlled trial (RCT) (not mentioned in Kerimoglu’s et al. [1]), Chang and colleagues [2] compared efficacy and efficiency of Cetrorelix and found to be 0.2 and 0.15 mg, respectively; they concluded that even for Asian women (for whom BMI is known to be lower than the Caucasian population), the lowest daily dose of Cetrorelix (in achieving satisfactory pituitary down-regulation) was 0.2 mg, and thus stated that daily administration of 0.15 mg ‘is not suitable’ for pituitary down-regulation. In addition to this, Chen et al. [3] also suggest that for Asian population ‘the lowest effective daily dosage is that of 0.2 mg’ and not 0.25 mg; even if one disregards the design of the study (non-randomized observational), that dose is closer to the ‘established’ one (0.25 mg) than the dosage of 0.125 mg suggested by Kerimoglu et al. [1]. Closely related to this are the findings of a more recent and larger retrospective study by Hsieh et al. [4]. That study concludes that ‘even for individuals with lower body weight (\50 kg), participants required 0.25 mg Cetrorelix daily. Furthermore, Tzeng’s study protocol [5], mentioned in Kerimoglu’s et al. [1], is quite different from daily Cetrorelix administration of 0.125 mg as it depends on leading follicular size; however, even with that protocol, the mechanism for LH-surge avoidance (which is used in 3 patients to end with the one LH surge that is mentioned in the paper) was the increase of the Cetrorelix dose to 0.25 mg/day. Finally, we should acknowledge the (potential) first ‘dose-finding’ study by Albano et al. [6], which concluded that ‘the minimal effective dose of Cetrorelix’ to prevent premature LH surge is 0.25 mg/daily. If a decrease in dosage is to be considered, further larger RCTs need to be conducted before we can move with confidence, to change in current clinical practice. T. Kalampokas Division of Applied Health Sciences, Assisted Reproduction Unit, University of Aberdeen, Aberdeen, UK

Prospective incorporation of vitrified embryo transfer (VFET) cycles into standard patient care: time to re-educate physicians & patients

In controlled ovarian hyperstimulation (COH) cycles, we believe that blastocyst (BL) vitrification (VTF) improves implantation success by allowing for optimum uterine conditions to exist. We aimed to show that VFET-BL cycles, with or without euploidy determination, improves pregnancy outcomes compared to fresh ET cycles.

Can oocyte vitrification improve art outcomes in low responder patients (LRP) stimulated with clomiphene citrate (CC)?

To assess the outcomes of a new strategy for (LRP): oocyte vitrification(OV) versus fresh oocytes. Case-control study. We included 22 patients with low response or cancelled cycles during 2011-2012 (vitri group). We propose them 3 ovulation induction cycles with (CC), gonadotrophin and GnRH antagonist, followed by oocyte collection and vitrification. In next cycles we thawed and fertilized oocytes by ICSI and transfer at least one embryo to a receptive endometrium. We evaluated also 49 (LRP) who underwent short protocol ovarian stimulation with GnRH agonists and Gonadotrophins (control group) in the same period. Statistical analysis: T- test. In the Vitri group (n=22) we completed 39cycles (1.77 cycles/patient) and we obtained 97 oocyte (4.4 occytes/patient). 13 patients got their oocytes warmed and fertilized. We thawed 58 oocytes (4.5 occytes/patient). Oocyte survival was 79,3% (46/58) and fertilization rate was 78% (36/46). 12 patients reached embryo transfer (92%, 12/13) transfering 2.8 embryos/patient. Pregnancy rate(PR)/patient was 53,8% (7/13) and implantation rate(IR) 24% (7/29). We obtained 7 clinical pregnancies (4 healthy new borns, 1 ongoing pregnancy and 2 miscarriages). The results in the control group were: cancelation rate 28.5% (14/49), total oocytes: 71 (2 occytes/patient), fertilization rate: 79% (56/71), transferred embryos/patient:1.7, (IR):19% (10/53),(PR)/patient: 20% (10/49) per oocyte retrieval: 28% (10/35). We obtained 10 pregnancies (3 miscarriages and 7 newborns). Patients age 38.2 and HAM levels 0.98 ng/ml in Vitri Group did not show significant difference with the control group 35 years and 0.94 ng/ml. (OV) allows us to obtain an oocyte pool from consecutive controlled ovarian hyperstimulation cycles, thawing them later when endometrium has been prepared. Using this strategy we avoided cycle cancellation and we improved (LRP) chances to reach embryo transfer as well as their pregnancy rate.

Acute respiratory failure following ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome is a serious and potentially life-threatening physiological complication that may be encountered in patients who undergo controlled ovarian hyperstimulation cycles. The syndrome is typically associated with regimes of exogenous gonadotropins, but it can be seen, albeit rarely, when clomiphene is administered during the induction phase. Although this syndrome is widely described in scientific literature and is well known by obstetricians, the knowledge of this pathological and potentially life-threatening condition is generally less than satisfactory among physicians. The dramatic increase in therapeutic strategies to treat infertility has pushed this condition into the realm of acute care therapy. The potential complications of this syndrome, including pulmonary involvement, should be considered and identified so as to allow a more appropriate diagnosis and management. We describe a case of a woman with an extremely severe (Stage 6) ovarian hyperstimulation syndrome who presented ascites, bilateral pleural effusion and severe respiratory failure treated with non-invasive ventilation. The patient was admitted to the intensive care unit because of severe respiratory failure, ascites, and bilateral pleural effusion due to ovarian hyperstimulation syndrome. Treatment included non-invasive ventilation and three thoracentesis procedures, plus the administration of albumin, colloid solutions and high-dose furosemid. Severe form of ovarian hyperstimulation syndrome is observed in 0.5-5% of the women treated, and intensive care may be required for management of thromboembolic complications, renal failure and severe respiratory failure. Pulmonary intensive care may involve thoracentesis, oxygen supplementation and, in more severe cases, assisted ventilation. To our knowledge, there have been only two studies in English language medical literature that describe severe respiratory failure treated with non-invasive ventilation.

Fertilization and pregnancy potential of immature oocytes from stimulated intracytoplasmic sperm injection cycles

ObjectiveWe evaluated the fertilization potential of immature oocytes obtained from controlled ovarian hyperstimulation cycles of patients undergoing ICSI.MethodsWe retrospectively analyzed 463 ICSI cycles containing at least one immature oocyte at oocyte denudation. ICSI was performed on mature oocytes at oocyte denudation (metaphase-II [MII] oocytes) and the oocytes that extruded the first polar body between oocyte denudation and ICSI (MI-MII oocytes). Fertilization and early embryonic development were compared between MII and MI-MII oocytes. To investigate the pregnancy potential of MI-MII oocytes, the pregnancy outcome was analyzed in 24 ICSI cycles containing only immature oocytes at retrieval.ResultsThe fertilization rate of MI-MII oocytes (37.0%) was significantly lower than that of MII oocytes (72.3%). The rates of delayed embryos and damaged embryos did not significantly differ. Eighty-one immature oocytes were retrieved in 24 cycles that retrieved only immature oocytes and 61 (75.3%) of them were in the MI stage. ICSI was performed on 36 oocytes (59.0%) that extruded the first polar body before ICSI and nine MI-MII oocytes (25.0%) were fertilized. Embryo transfers were performed in five cycles. Pregnancy was observed in one cycle, but it ended in biochemical pregnancy.ConclusionIn ICSI cycles, oocytes that extruded the first polar body between denudation and ICSI can be used as a source of oocytes for sperm injection. However, their fertilization and pregnancy potential are lower than that of mature oocytes. Therefore, ovarian stimulation should be performed carefully for mature oocytes obtained at retrieval, especially in cycles with a small number of retrieved oocytes.

The levels of hepatocyte growth factor in serum and follicular fluid and the expression of c-Met in granulosa cells in patients with polycystic ovary syndrome

To evaluate the levels of hepatocyte growth factor (HGF) in follicular fluid (FF) and the expression of c-Met in granulosa cells (GCs) with respect to the quality of the oocyte and embryo both in patients with polycystic ovary syndrome (PCOS) and in the normal ovary during controlled ovarian hyperstimulation cycles. Prospective controlled study. University hospital. Fifty-nine women undergoing IVF treatment (of whom 21 had PCOS and 38 were in the control group). A total of 168 FF samples were collected at the time of oocyte retrieval. The HGF levels were measured by ELISA, and the mRNA expression of c-Met in GCs was detected by real-time polymerase chain reaction. The predictive values of HGF levels in serum and FF and the mRNA expression of c-Met in GCs for successful fertilization and oocyte-embryo quality. The levels of HGF in serum and FF and the c-Met expression in GCs were similar between the PCOS and control groups. Granulosa cells of fertilized oocytes (2PN) had a significantly higher level of c-Met expression than that in oocytes that failed to fertilize. The mean HGF level in FF was significantly higher in the grade 1 embryos than in the grades 2-4 embryos. This study suggests that HGF/c-Met signaling may be a crucial determinant of fertilization success.

Controlled ovarian hyperstimulation (COH) cycles may benefit from vitrification of all day 5 PGS-biopsied blastocysts

Array CGH-PGS technology offers rapid, complete chromosomal analysis for aneuploidy screening and sex determination. Interlaboratory next day results from Day 5 BL biopsy accommodates a fresh ET by noon on Day 6. The objective of this study was to assess whether the delayed ET was suboptimal to pregnancy outcome and what factors may be involved.

A comparison of in-vitro maturation versus antagonist protocols for in-vitro fertilization in women with polycystic ovarian syndrome

Polycystic ovarian syndrome (PCOS) patients are at increased risk of ovarian hyperstimulation syndrome (OHSS) in controlled ovarian hyperstimulation cycles. Inducing oocyte maturation with Gonadotropin Releasing Hormone (GnRH) agonists, in patients stimulated with GnRH antagonist protocols can prevent this complication. In these protocols, ovarian stimulation requires large amounts of gonadotropins. Earlier retrieval of immature oocytes followed by in vitro maturation (IVM) may be a potential alternative intervention for these patients, without exposure to gonadotropins and the risk of OHSS.

Influence of controlled ovarian hyperstimulation on uterine peristalsis in infertile women

Is there a difference in the characteristics of uterine peristalsis in natural and controlled ovarian hyperstimulation (COH) cycles? COH significantly changed the uterine peristaltic pattern. In natural menstrual cycles, the periodic changes of uterine peristalsis are closely related to the reproductive process. This is a prospective cohort study with a total of 64 subjects involved. The study was performed between May 2011 and August 2011. Sixty-four infertile women with regular, ovulatory menstrual cycles underwent follicular tracking in one natural cycle and after ovarian stimulation (GnRH-agonist down-regulation) in the subsequent cycle (COH). Three time points were studied in both cycles: at LH surge/HCG plus 1 day, ovulation/oocyte retrieval and 2 days after ovulation/retrieval. The study was performed in an IVF center of the university-affiliated Xiangya hospital. Uterine peristaltic wave frequency was 1.31 times higher in the COH than in the natural cycle (P< 0.01). At all three time points in the COH cycle, waves moving from the cervix to fundus dominated, comprising 80-90% of the wave types observed, while 'no activity' was more frequently observed in the natural cycle. The wave frequency was positively correlated with the level of serum estradiol (E(2)) (r= 0.30; P< 0.01) and negatively correlated with the progesterone level (r= -0.48; P< 0.01) for the physiological range of steroid levels. No correlation was found between the wave frequency and supraphysiological concentrations of E(2) or progesterone. The two observers were not independent and this was a limitation of the study. Quantitative measurements of wave amplitude in the different cycles should be compared in future research. Uterine peristalsis was much higher in the COH cycle than in the natural cycle. The endometrial movements did not weaken to the natural level before embryo transfer, even with high levels of progesterone. The wave frequency was positively correlated with serum E(2) level and negatively correlated with that of progesterone within the physiological range. No correlation was found between the wave frequency and supraphysiological concentrations of E(2) and progesterone.

Live birth after in vitro maturation and vitrification of immature oocytes retrieved from conventional IVF cycle: a case report

Oocyte cryopreservation is gaining increased recognition as a viable alternative to embryo freezing since this technique satisfied several concerns about ethical, religious and social constraints that are associated with the creation and storage of embryos, and allowed donated oocytes to be used following quarantine in a more cost-effective manner and offered women an ideal modality to not only preserve their fertility but also their reproductive autonomy [1]. Despite this, oocyte cryopreservation is technically challenging and it has been more than two decades since the first successful report of oocyte cryopreservation using the slow-freezing method [2]. Although additional reports of successful oocyte freezing and normal pregnancies followed, the slow-freezing method did not become a routine IVF procedure because of its inefficiency and inconsistency [3]. In contrast, vitrification has been reported more recently as an alternative cryopreservation method that is characterized by simplicity, low cost, and high efficiency for cryopreserving both oocytes and embryos. Oocyte vitrification offers increased success rates in comparison to the slow-freezing method. There are now over 1500 live births resulting from IVF oocyte vitrification reported in the literature [4–6]. In addition, several IVF centers in the world have reported pregnancy rates similar to those of standard fresh IVF treatments [7, 8]. However, very few live births have been reported after cryopreservation of immature oocytes either before in vitro maturation (IVM) [9] or after IVM [10, 11]. The first live birth after slow-freezing of the immature oocytes retrieved from conventional IVF cycles was reported in 1998 [9]. Recently, 4 pregnancies with live birth from immature oocytes retrieved in a natural menstrual cycle, followed by IVM and cryopreservation of the oocytes by vitrification have been reported [10, 11]. However, there has been no report whether the mature oocytes produced by IVM of immature oocytes obtained from conventional IVF cycles can be vitrified and develop into viable embryos. In this case report, we present a pregnancy resulting from transfer of vitrified IVM oocytes generated from immature oocytes of a conventional IVF cycle. To the best of our knowledge, this is the first report of a live birth from vitrification of oocytes produced by IVM of immature oocytes derived from the controlled ovarian hyperstimulation (COH) cycles of a patient in the oocyte donation program.

Clinical outcome of fresh and vitrified-warmed blastocyst and cleavage-stage embryo transfers in ethnic Chinese ART patients

ObjectivesThis study sought to evaluate the outcome of fresh and vitrified-warmed cleavage-stage and blastocyst-stage embryo transfers in patients undergoing ART treatment within an ethnic Chinese population.Study designWe compared the clinical results of embryo transfer on the 3rd (cleavage stage) or 5th (blastocyst stage) day after oocyte retrieval, including clinical pregnancy rates, implantation rates and multiple pregnancy rates.ResultsOur data showed that blastocyst transfer on day 5 did not significantly increase clinical pregnancy rate (41.07% vs 47.08%, p>0.05) and implantation rate (31.8% vs 31.2%, p>0.05) in patients under 35 years of age, in comparison with day 3 cleavage stage embryo transfer. In patients older than 35 years of age, the clinical pregnancy rate after blastocyst transfer was slightly decreased compared with cleavage stage embryo transfer (33.33% vs 42.31%, p>0.05). Unexpectedly, It was found that vitrified-warmed blastocyst transfer resulted in significantly higher clinical pregnancy rate (56.8%) and implantation rate (47%) compared with fresh blastocyst transfer in controlled stimulation cycles (41.07% and 31.8%, respectively). For patients under 35 years of age, the cumulative clinical pregnancy rate combining fresh and vitrified-warmed blastocyst transfer cycles were significantly higher compared to just cleavage-stage embryo transfer (70.1% versus 51.8%, p<0.05). However, the cumulative multiple pregnancy rates showed no significant difference between the two groups.ConclusionsIn an ethnic Chinese patient population, fresh blastocyst transfer does not significantly increase clinical pregnancy rate. However, subsequent vitrified-warmed blastocyst transfer in a non-controlled ovarian hyperstimulation cycle dramatically improves clinical outcomes. Therefore, blastocyst culture in tandem with vitrified-warmed blastocyst transfer is recommended as a favourable and promising protocol in human ART treatment, particularly for ethnic Chinese patients.

Fertility preservation in young patients before allogeneic haematopoietic SCT

As the long-term survival rate of patients receiving HSCT increases, quality of life issues, including the possibility to parent children, deservedly gain ever more attention. We therefore fully endorse the authors’ appeal for fertility preservation in this patient group, and appreciate their efforts to raise awareness of this issue in the medical community. We would like to take the opportunity to emphasise that the options for fertility preservation for this group are restricted. To illustrate this notion we would like to supplement their paper with a brief discussion of the available options. For male patients, fertility preservation is relatively easy, provided that their HSCT starts after puberty, that is the onset of semen production. Semen cryopreservation is a readily available option that can be offered in practically every fertility centre and can be performed with no or hardly any delay in the treatment. For pre-pubertal boys, unfortunately, there are to date no options. The cryopreservation of spermatogonial stem cells with the aim of retransplanting them after cure resulting in the initiation of spermatogenesis, is currently being investigated. 2 For female patients the situation is more complicated. Considering the young age of most patients, emergency in vitro fertilisation followed by cryopreservation of the generated embryos will in the majority of cases not be an option, as this requires a stable relationship with a male partner. The cryopreservation (by means of vitrification) of oocytes is the next logical alternative. This option is suitable for postpubertal girls and requires hormonal ovarian hyperstimulation to increase the number of mature oocytes that can be obtained. 3 Depending on the number of oocytes one wishes to obtain, one or more cycles of hyperstimulation may be required. As a consequence, treatment will have to be postponed for at least 14 days or up to several months. It should be determined for each patient individually what period of postponement of the treatment is acceptable. In prepubertal girls, or in those cases where delay of the treatment is not advisable, immature oocytes may be obtained and vitrified. These oocytes have to be matured in vitro ,b efore they can be used for fertilisation at a later stage of life. To the

Dynamique de l’index de vascularisation et de flux dans la phase préovulatoire de l’hyperstimulation ovarienne contrôlée. Relation avec le taux de conception

ObjectivesTo study the evolution of subendometrial vascularization flow index (VFI) in controlled ovarian hyperstimulation (COH+IIU) cycles and compare its dynamic changes in pregnant and non pregnant women. Patients and methodsThis is a retrospective study on 61 couples. To determine the profile of IVF just before ovulation, patients had 3D-Power Doppler angiography (3D-PDA) in this precise preovulatory phase. ResultsWe observed a decreasing profile of VFI in 52% (32/61) of the main group cycles, in 45% (14/31) of the subgroup with spontaneous peak of LH (luteinizing hormone), and in 60% (18/30) of the hCG (human chorionic gonadotropin) trigger subgroup. There were ten conceptions, (10/61, 16.4%), including eight (8/32, 30%) that were associated with a decreasing profile of VFI versus two (2/29, 7%) that were associated with an increasing profile (NS). In the detection of LH peak subgroup, we observed five conceptions (5/14, 36%) associated with a decreasing profile versus one conception (1/17, 6%) associated with an increasing profile of VFI (OR: 8.3; confidence interval [CI] 95%: 0.8–444; P=0.06 in favor of a of decreasing VFI profile). In the hCG subgroup, there were three conceptions in the decreasing VFI profile (3/18, 17%) and one conception with increasing VFI (1/12, 17%, P=0.6). Discussion and conclusionIn controlled ovarian hyperstimulation, a decreasing VFI profile is more common compared to an increasing one. Such au profile seems to be associated with a higher conception rate in cycles with spontaneous LH surge.

Modified natural-cycle in vitro fertilization should be considered as the first approach in young poor responders

The use of modified natural-cycle invitro fertilization (IVF) is a valuable alternative to controlled ovarian hyperstimulation in young poor responders and should be considered in patients who require IVF and demonstrate endocrinologic evidence of ovarian aging and in those who have had one or two canceled controlled ovarian hyperstimulation cycles.

Site-specific endometrial injury improves implantation and pregnancy in patients with repeated implantation failures

BackgroundTo test whether a site-specific hysteroscopic biopsy-induced injury in the endometrium during the controlled ovarian hyperstimulation cycle improves subsequent embryo implantation in patients with repeated implantation failure, a total of 30 patients who have had good responses to controlled ovulation stimulation but have failed to achieve pregnancy after two or more transfers of good-quality embryos were recruited in this prospective study.MethodsA single, site-specific hysteroscopic biopsy-induced injury was generated on the posterior endometrium at midline 10-15 mm from the fundus during the D4-D7 period of the ongoing controlled ovarian hyperstimulation cycle in six patients.ResultsPatients received endometrial biopsy protocol achieved a pregnancy rate of 100%. By contrast, only 46% of patients with similar clinical characteristics (N = 24) achieved pregnancy without the hysteroscopic biopsy-induced endometrium injury (p < 0.05).ConclusionsOur proof-of-concept study demonstrates that a site-specific hysteroscopic endometrium injury performed during the ongoing in vitro fertilization (IVF) cycle, instead of injuries received during prior cycles, significantly improves clinical outcomes in patients with repeated implantation failure.

Expanding reproductive lifespan: a cost-effectiveness study on oocyte freezing

The average age of women bearing their first child has increased strongly. This is an important reproductive health problem as fertility declines with increasing female age. Unfortunately, IVF using fresh oocytes cannot compensate for this age-related fertility decline. Oocyte freezing could be a solution. We used the Markov model to estimate the cost-effectiveness of three strategies for 35-year-old women who want to postpone pregnancy till the age of 40: Strategy 1: women undergo three cycles of ovarian hyperstimulation at age 35 for oocyte freezing, then at age 40, use these frozen oocytes for IVF; Strategy 2: women at age 40 attempt to conceive without treatment; and the reference strategy: women at age 40 attempt to conceive and, if not pregnant after 1 year, undergo IVF. Sensitivity analyses were carried out to investigate assumptions of the model and to identify which model inputs had most impact on the results. Oocyte freezing (Strategy 1) resulted in a live birth rate of 84.5% at an average cost of €10,419. Natural conception (Strategy 2) resulted in a live birth rate of 52.3% at an average cost of €310 per birth. IVF (the reference strategy) resulted in a cumulative live birth rate of 64.6% at an average cost of €7798. The cost per additional live birth for the oocyte freezing strategy was €13,156 compared to the IVF strategy. If at least 61% of the women return to collect their oocytes, and if there is a willingness to pay €19,560 extra per additional live birth, the oocyte freezing strategy is the most cost-effective strategy. Oocyte freezing is more cost effective compared to IVF, if at least 61% of the women return to collect their oocytes and if one is willing to pay €19,560 extra per additional live birth. Our Markov model shows that, considering all the used assumptions, oocyte freezing provides more value for money than IVF.

Are all human-derived follicle-stimulating hormone products the same? A systematic review and meta-analysis using direct and adjusted indirect analyses, to determine whether Fostimon® is more efficient than Metrodin-HP®

Background. Randomized trials (RCTs) and systematic reviews have challenged the claim for superiority of recombinant follicle-stimulating hormone (recFSH) compared with human-derived FSH (hFSH). Even so, much of the evidence comes from unavailable products. If the efficacy of the currently available Fostimon® is superior, the off-market Metrodin-HP®, then data from the latter should not be used, gauge of the former. Methods. Electronic/hand searches were performed to identify RCTs comparing Fostimon® vs. Metrodin-HP® or either product with recFSH. Primary outcomes were live-birth rate (LBR), ongoing pregnancy rate (OPR), and OPR/LBR. Secondary outcomes were clinical pregnancy rate (CPR), multiple pregnancy rate (MPR), ovarian hyperstimulation syndrome (OHSS), abortion rates, and cycle demographics. Data were extracted, allowed for an intention-to-treat analysis, and meta-analyzed using combined direct/adjusted indirect methods. Results. Twenty-two RCTs met the inclusion criteria: Fostimon® vs. Metrodin-HP® (n = 2); Fostimon® vs. recFSH (n = 8); and Metrodin-HP® vs. recFSH (n = 12). LBR (odds ratio = 1.72; 95% confidence interval = 1.05–2.80), OPR/LBR, and CPR were all significantly higher favoring Fostimon®. OPR, MPR, OHSS, and miscarriage rates were not significantly different. Pooled results for cycle demographics were not reported due to high heterogeneity. Conclusions. Fostimon® is superior to Metrodin-HP® regarding clinical outcomes. Therefore, care should be taken not to assume that all hFSH products have the same efficacy.

Cancellation of fresh embryo transfer: A future perspective

Abstract The implantation of embryo depends on the quality of the embryo and the receptivity of the endometrium. While the factors affecting embryo quality were optimized, the implantation rates did not reach the desirable levels. This directs the blaming for endometrial receptivity which already has been affected by supra-physiological levels of hormone, namely estradiol in controlled ovarian hyperstimulation (COH) cycle. On the other hand, cryopreservation, especially the vitrification method, has been highly improved to give almost the same results of fresh state, in addition to decreased rate of blastogenesis birth defects. All these encourage us to put our opinion to overcome the problem of endometrial receptivity by cancellation of the fresh embryo transfer (fresh ET) and to perform the frozen–thawed embryo transfer (FET) in cases of excessive response to COH.