Ovulation Induction

In the last decades, several steps have been made aiming at rendering human IVF more successful on one side, more tolerable on the other side. The "mild" ovarian stimulation approach, in which a lower-than-average dose of exogenous gonadotropins is given and gonadotropin treatment is started from day 2 to 7 of the cycle, represents a significant step toward a more patient's friendly IVF. However, a clear view of its virtues and defects is still lacking, because only a few prospective randomized trials comparing "mild" vs. conventional stimulation exist, and they do not consider some important aspects, such as, e.g., thawing cycles. This review gives a complete panorama of the "mild" stimulation philosophy, showing its advantages vs. conventional ovarian stimulation, but also discussing its disadvantages. Both patients with a normal ovarian responsiveness to exogenous gonadotropins and women with a poor ovarian reserve are considered. Overall, we conclude that the level of evidence supporting the use of "mild" stimulation protocols is still rather poor, and further, properly powered prospective studies about "mild" treatment regimens are required.

In the present study, we examined the outcome of assisted reproductive technology cycles in patients with or without baseline ovarian cysts following gonadotrophin-releasing hormone analogs administration. Materials and Methods: Three-hundred and fifty-six patients who had undergone assisted reproductive technology treatment were enrolled in the study. The patients, all of who had undergone cyst aspiration prior to ovarian stimulation, were grouped into two groups according to the absence or presence of ovarian cysts. These two groups were compared on the basis of the clinical pregnancy rates, the baseline E2 levels, the total follicle stimulating hormone ampules used, the total number of days of induction, the maximum E2 levels, the number of oocytes retrieved, the fertilization rates and the number of embryos available for transfer per controlled ovarian hyperstimulation cycle. Results: The number of ampules used for induction was significantly higher in the cyst group 37.2 ± 13.0, 32.1 ± 11.7, respectively, ( P = 0.001). The number of total induction days was also longer in the cyst group 9.7 ± 2.2, 8.9 ± 1.6, respectively, ( P = 0.001). There was no difference between the mean E2 levels measured on the human chorionic gonadotropin administration days ( P = 0.339). There was also no difference in terms of the number of oocyte retrieved ( P = 0.846). The number of embryos transferred did not differ statistically between the groups ( P = 0.233). Finally, there was no significant difference between the groups according to the clinical pregnancy rates 25.3%, 30.7%, respectively, ( P = 0.218). Conclusion: Baseline ovarian cysts have a negative impact on the quality of ovarian hyperstimulation procedure; however, they have no negative effect on the pregnancy rates in IVF cycles.

Objective: To compare the effectiveness of letrozole and clomiphene citrate (CC) in ovulatory patients with borderline male factor infertility, early stage endometriosis, and unexplained infertility. Design: Prospective quasi-randomized trial. Setting: University infertility clinic. Patient(s): Forty-six consecutive patients with ovulatory infertility were recruited. Twenty-five patients (67 cycles) were given CC and 21 patients (52 cycles) were given letrozole. Both drugs were given orally on days 3-7 of menses. Intervention(s): Letrozole, CC, ovulation induction, IUI, timed intercourse. Main Outcome Measure(s): Number of follicles, endometrial thickness, and pregnancy rates. Result(s): The median serum E 2 concentration on the day of hCG administration in the letrozole and CC groups were 191.5 pmol/L and 476.0 pmol/L, respectively. The median endometrial thickness on the day of hCG were 8 mm in both groups. Ovulation occurred in 81% (42/52) of the letrozole-treated and 85% (57/67) of the CC-treated patients. Pregnancy rate (PR) per cycle was 9% (5/52) in the letrozole group and 12% (8/67) in the CC group. Conclusion(s): Letrozole and CC have comparable effectiveness in ovulatory patients with borderline male factor infertility, early stage endometriosis, and unexplained infertility. (Fertil Steril 2006;85:1045-8.

Background: It is well known that many anurans do not reproduce easily in captivity. Some methods are based on administration of mammalian hormones such as human chorionic gonadotropin, which are not effective in many frogs. There is a need for simple, cost-effective alternative techniques to induce spawning.

Objective: To investigate the incidence, risk factors, and sonographic findings of maternal ovarian torsion in pregnancy. Design: Retrospective study. Setting: Department of Obstetrics/Gynecology of a tertiary referral center. Patient(s): Thirty-three pregnant women with 38 episodes of surgically proven torsion between the years 1993 to 2007. Intervention: Surgical confirmation and treatment of torsion. Main Outcome Measure(s): Clinical and sonograpgic findings of ovarian torsion in pregnancy.

Scientists are able to advance the frontiers of human reproduction by employing a variety of molecular biological techniques to understand the biological processes intricately linked to oocyte and ovarian follicle development. Despite an abundance of knowledge concerning essential pathways which may have critical roles in oogenesis and folliculogenesis, the repertoire of medications to treat female fertility problems remains limited to a few classes of drugs involved in the induction or suppression of folliculogenesis and ovulation; many of which are not specific in their drug actions and can give rise to complications during clinical application. This paper aims to review biomolecules and pathways (e.g. PI3K, WNT, MAPK) pertinent to ovarian follicular development and active in human oocytes, including those involved in communication between somatic cells within the ovary (cumulus cells, granulosa cells and thecal cells) and the oocyte itself. These biomolecules which are involved in the nuclear and cytoplasmic maturation of oocytes and the control of ovarian folliculogenesis have potential as targets for improved ovarian stimulation, optimisation of oocyte maturation, and as biomarkers of oocyte viability assessment.

Objective: To identify dominant predictors of clinical pregnancy in IVF cycles. Design: Retrospective study. Setting: Private fertility center. Patient(s): The study included 580 fresh autologous IVF cycles with blastocyst transfer. Intervention(s): None. Main Outcome Measure(s): Clinical pregnancy rate.

Purpose The purpose of this study was to identify trends in gonadotropin therapy in patients undergoing in vitro fertilization (IVF) treatment worldwide. Methods Retrospective evaluation utilizing the results of a Web-based survey, IVF-Worldwide (www.IVF-worldwide. com) was performed. Results Three hundred fourteen centers performing a total of 218,300 annual IVF cycles were evaluated. R e s p o n d e n t s r e p r e s e n t i n g 6 2. 2 % o f c y c l e s (n = 135,800) did not believe there was a difference between urinary and recombinant gonadotropins in terms of efficacy and live birth rate. Of the respondents, 67.3% (n = 146,800) reported no difference between recombinant and urinary formulations in terms of short-term safety and risk of ovarian hyperstimulation syndrome. In terms of long-term safety using human urinary gonadotropins, 50.6% (n = 110,400) of respondents believe there are potential long-term risks including prion disease. For 95.3% of units (n = 208,000), the clinician was the decision maker determining which specific gonadotropins are used for IVF. Of the units, 62.6% (n = 136,700) identified efficacy as the most important factor in deciding which gonadotropin to prescribe. While most (67.3%, n = 146,800) were aware of new biosimilar recombinant FSH products entering the market, 92% (n = 201,000) reported they would like more information. A fraction of respondents (25.6%, n = 55,900) reported having experience with these new products, and of these, 80.3% (n = 46,200) reported that they were similar in efficacy as previously used gonadotropins in a similar patient group. Conclusions Respondents representing the majority of centers do not believe a difference exists between urinary and recombinant gonadotropins with respect to efficacy and live birth rates. While many are aware of new biosimilar recombinant FSH products entering the market, over 90% desire more information on these products.

Objective: To analyze if oocytes can be obtained in all patients before cancer treatment within 2 weeks by initiating ovarian stimulation during the follicular or luteal phase. Design: Prospective controlled multicenter trial. Setting: Four university-based centers. Patient(s): Forty cancer patients before chemotherapy. Intervention(s): Twenty-eight patients were stimulated with gonadotropins in the follicular phase (group I). In 12 patients (group II), ovarian stimulation was initiated in the luteal phase, and these received GnRH antagonists and recombinant FSH. In 14 patients, 143 oocytes were further processed for fertilization by intracytoplasmic sperm injection (ICSI). Main Outcome Measure(s): Number of oocytes aspirated after ovarian stimulation, cumulative FSH/hMG dosage, viability and maturity of oocytes, and fertilization rate by ICSI. Result(s): Patients in group I (age 27.6 AE 4.9 yrs) were stimulated on average for 10.6 days, and patients in group II (age 31.2 AE 5.7 yrs) for 11.4 days. Total amount of FSH was on average 2,255 IU (I) and 2,720 IU (II) per patient. Average and median numbers of aspirated oocytes were, respectively, 13.1 and 11.5 (I) versus 10.0 and 8.5 (II); 83.7% (I) and 80.4% (II) of the oocytes were mature and viable and could be treated by ICSI. Fertilization rate was 61.0% (I) versus 75.6% (II). Conclusion(s): This pilot study suggests that oocytes can be obtained before cancer treatment efficiently irrespective of the phase of the menstrual cycle.

Indications for estrus induction in the bitch include missed breeding opportunities or conception failure, the treatment of primary or secondary anestrus and synchronization of ovulation for embryo transfer programs. Reported methods for canine estrus induction include the use of synthetic estrogens (diethylstilbesterol), dopamine agonists (bromocryptine and cabergoline), GnRH agonists (lutrelin, buserelin, fertirelin, deslorelin, and leuprolide) and exogenous gonadotropins (luteinizing hormone, follicle stimulating hormone, human chorionic gonadotropin, pregnant mare serum gonadotropin, and human menopausal gonadotropin). These methods vary widely in efficacy of inducing estrus, as well as in the fertility of the induced estrus. The applicability of some of these methods for clinical practice is questionable. This review will summarize published reports on estrus induction and synchronization in bitches and summarize preliminary results using a long-acting injectable preparation of deslorelin.

Transcervical embryo collection is used routinely in the bovine species throughout the world to collect Day 6 to Day 9 embryos (early embryos) for genetic selection. For research purposes, however, the collection of embryos at later stages of pregnancy, i.e., Days 12 to 21 (late embryos), is needed. So far, for the recovery of late embryos, females are euthanized and embryo collection is performed after recovery of the genital tract. To reduce the number of animals used and still provide valuable material for embryo research, we have therefore developed a transcervical technique to collect late embryos. The objective of this study was to compare embryo recovery results at early and late stages within our laboratory. Altogether, 232 cows were used for this study. One hundred forty-five flushes were performed to collect embryos from Days 6 to 9, and 251 flushes were performed to collect embryos from Days 12 to 21. For the early embryos, a classical three-way collection equipment was used. To collect the late embryos, the same equipment was used, but the extensible flexible catheter that goes inside the external rigid catheter was removed, so that larger embryos could be collected through the remaining larger hole (two-way collection). All females were submitted to ovum pick up to remove the dominant follicle and were subsequently superovulated with FSH. Luteolysis was induced 48 hours before artificial insemination. Two artificial inseminations were performed with frozen semen, 48 and 56 hours after PGF2a injection. Before embryo collection, cows were treated with an epidural injection of a local anesthetic drug. The presence of CL was checked, and they were counted by rectal palpation. For all collections, the cervix was prepared with the initial introduction of a dilator. Then, the catheter was introduced in one horn, and the cuff was inflated as low as possible. For the collection of late embryos, the flushing solution (30 mL) was injected slowly twice to suspend the embryos before flushing the horn with 500 mL, and the same operation was performed on the second horn. There was no significant difference in the number of embryos collected per flush in the early-and latestage (758 embryos collected, 5.22 AE 6.02 per flush vs. 1238 embryos collected, 4.93 AE 5.07 per flush, respectively). The number of embryos collected per CL, however, was significantly lower in the early versus late group (0.39 AE 0.32% vs. 0.44 AE 0.34%, respectively). The late collection allowed the retrieval of full conceptuses (embryonic and extraembryonic tissues), even at very late stages such as Days 18 to 21. Careful collection is needed, however, so that conceptuses are not damaged or torn: the horn must be * Corresponding author. Tel.: þ33 1 34 65 24 19; fax: þ33 1 34 65 23 64. Theriogenology xxx (2015) 1-9 massaged gently and the flush should be ideally recovered in one single flow. This technique is a powerful tool to collect the late-stage embryos for research purposes. Because it is not traumatic, animals can be used again for the same procedure.

Purpose To evaluate the impact of stimulating the endometrium with high-grade blastocyst culture supernatant (SEHB) perfusion before blastocyst transfer (BT) on implantation rate, pregnancy rate, and pregnancy outcome in ICSI cycles. Materials and methods Ninety-four infertile couples who were referred to the Valiasr department of Imam Hospital complex between January 2010 and March 2011 enrolled in this randomized clinical trial. They were randomly divided into only BT or SEHB groups. Implantation rates, pregnancy rates, abortion, preterm and term delivery rates were compared between the two groups. Results Implantation rates and pregnancy rates did not differ significantly between the two groups. The abortion rate was significantly higher in the BT only group while term delivery was significantly higher in SEHB group. Odds ratios of term delivery and abortion were 4.5 (p = 0.001) and 0.3 (p = 0.04), respectively. Conclusion The SEHB application may improve pregnancy outcome in infertile couples who are candidates for the ICSI reproductive method.

The effects of estradiol benzoate (EB) and estradiol cypionate (EC) on induction of ovulation after a synchronized LH surge and on fertility of Bos indicus females submitted to timed AI (TAI) were evaluated. In Experiment 1, ovariectomized Nelore heifers were used to evaluate the effect of EB (n ϭ 5) and EC (n ϭ 5) on the circulating LH profile. The LH surge timing (19.6 and 50.5 h; P ϭ 0.001), magnitude (20.5 and 9.4 ng/mL; P ϭ 0.005), duration (8.6 and 16.5 h; P ϭ 0.001), and area under the LH curve (158.6 and 339.4 ng/mL; P ϭ 0.01) differed between the EB and EC treatments, respectively. In Experiment 2 (follicular responses; n ϭ 60) and 3 (pregnancy per AI; P/AI; n ϭ 953) suckled Bos indicus beef cows submitted to an estradiol/progesterone-based synchronization protocol were assigned to receive one of two treatments to induce synchronized ovulation: 1 mg of EB im 24 h after progesterone (P4) device removal or 1 mg of EC im at P4 device removal. There was no difference (P Ͼ 0.05) between EB and EC treatments on follicular responses (maximum diameter of the ovulatory follicle, 13.1 vs. 13.9 mm; interval from progesterone device removal to ovulation, 70.2 vs. 68.5 h; and ovulation rate, 77.8 vs. 82.8%, respectively). In addition, P/AI was similar (P Ͻ 0.22) between the cows treated with EB (57.5%; 277/482) and EC (61.8%; 291/471). In conclusion, despite pharmacologic differences, both esters of estradiol administered either at P4 device removal (EC) or 24 h later (EB) were effective in inducing an LH surge which resulted in synchronized ovulations and similar P/AI in suckled Bos indicus beef cows submitted to TAI.

Polycystic ovary syndrome (PCOS) occurs in 6 to 10% of women during the reproductive age. Insulin resistance and compensatory hyperinsulinemia are currently two of the main factors involved in the etiopathogenesis of PCOS. The objective of the present review was to discuss the controversies related to the treatment of infertile women with PCOS and during their pregnancy, focusing on the European Society of Human Reproduction and Embryology (ESHRE) and the American Society for Reproductive Medicine (ASRM) current consensus.

Objective: The aim of the study was to evaluate if the diagnosis and treatment of uterine cavity abnormalities by hysteroscopy in patients undergoing IVF programme is of any value in improving clinical pregnancy outcome. Methods: 520 patients participated in this prospective randomized study and were classified into two groups. Group I (n = 265) without office hysteroscopy. Group II (n = 255) had office hysteroscopy and was sub classified into Group II a and Group II b. Group II a (n = 160) had normal hysteroscopic findings whereas Group II b (n = 95) had abnormal office hysteroscopy findings, which were corrected at the same time. Result: There was no difference in the mean number of oocytes retrieved, fertilization rate, and number of embryos transferred among the patients in different groups. Statistically significant difference was observed in terms of clinical pregnancy rates between Group I and Group II a (26.2 and 44.44%, P < 0.05), and Group I and Group II b (26.2 and 39.55%, P < 0.05), respectively. Conclusion: Patients with recurrent IVF embryo transfer failures after normal hysterosalpingography findings should also be reevaluated using hysteroscopy prior to further commencing IVF-embryo transfer cycles in order to enhance the clinical pregnancy rates.

The effect of exercise on mare reproductive efficiency was evaluated by comparing rates of embryo recovery from mares assigned to either an exercise regimen or a non-exercise (control) regimen. Exercised mares were worked daily for 30 min under average ambient conditions of >30 • C and >50% humidity. Mares were inseminated during estrus and subjected to uterine flush for embryo recovery on d 7 after ovulation for two consecutive cycles. After this, mares were allocated to the opposite group and allowed an estrous cycle without reproductive manipulation; then insemination and uterine flushing were conducted on two more consecutive cycles. Prostaglandin F 2␣ was administered on the day of uterine flush. Mare rectal temperature increased during exercise from a mean of 38 • C to a mean of 39.9 • C. Mares had ovulations from smaller follicles when exercised than they did under control conditions (39.8 ± 0.5 compared with 41.5 ± 0.5 mm diameter; P < 0.05), and had an increased time from PGF 2␣ administration to subsequent ovulation (8.47 ± 0.337 compared with 9.27 ± 0.294 d; P < 0.05). Embryo recovery from control mares was 22 of 35 (63%). Fewer embryos were recovered from exercised mares (11 of 32, 34%; P < 0.05). The proportion of embryos classified as Grade 1 tended to be less in exercised than in non-exercised mares (4 of 11, 36% compared with 16 of 22, 73%; P = 0.051). These data indicate that exercising mares in a hot and humid environment are associated with changes in ovarian follicle development and ovulation, and a reduction in embryo recovery.

Objective: To evaluate gonadotropin-releasing hormone (GnRH) agonist/antagonist conversion with estrogen priming (AACEP) in low responders with prior IVF failure. Design: Descriptive. Setting: Private practice. Patient(s): Women aged %42 with prior IVF attempts in which all embryos were <7 cells or >20% fragmentation on day 3 (n ¼ 137; <38: n ¼ 63; 38-42: n ¼ 74). In addition to unexplained poor response to stimulation (n ¼ 52), diagnoses included elevated follicle-stimulating hormone (FSH >9.0 mIU/mL; n ¼ 40), advanced age (>41 years; n ¼ 26), endometriosis (III-IV; n ¼ 12), and decreased ovarian reserve (AFC <5; n ¼ 7). Intervention(s): Patients received sequential GnRH agonist, low-dose GnRH antagonist, and estradiol valerate followed by recombinant FSH, 600 IU/day (n ¼ 72) or 750 IU/day (n ¼ 65). Main Outcome Measure(s): Pregnancy, ongoing gestation, implantation rates. Result(s): Although women aged <38 years and those on 600 IU/day produced more mature eggs and fertilized embryos than women aged 38 to 42 years, there were no differences in peak estradiol, endometrial lining, or embryos transferred. Outcomes were similar for all patients regardless of age or FSH dosage. Ongoing gestation rates were 27% (37 out of 137) for all patients, 25% (16 out of 63) for age <38 years, and 28% (21 out of 74) for ages 38 to 42 years. Conclusion(s): Women aged %42 years who are candidates for oocyte donation may still achieve pregnancy using their own eggs with the AACEP protocol. (Fertil Steril Ò 2008;89:342-7.

The aim of this review paper is to provide a scientific basis for the development of ovarian stimulation (OS) protocols for in vitro fertilization (IVF) in baboons. Firstly, the evidence available regarding OS for assisted reproduction in baboons is reviewed based on available published data, assessed by a Pub Med search of papers published between 1970 and 2008 using the following key words: baboon, assisted reproduction, IVF, embryo, oocyte. Secondly, we discuss how state-of-the-art or potentially new OS protocols used in humans and in rhesus monkeys may offer guidance for the development of standardized and reliable OS protocols for IVF in baboons. Based on this review and discussion, we conclude that more randomized trials are needed to improve standardization of OS protocols for IVF in baboons with respect to gonadotrophin type, dose, duration of stimulation, ultrasound monitoring, and time interval between ovulation trigger and oocyte retrieval.

La stimulation ovarienne et la ponction folliculaire en AMP présentent des risques qui doivent être envisagés afin de mieux les prévenir. Ces complications sont l'hyperstimulation ovarienne, les risques thromboemboliques et carcinologiques, les risques anesthésiques, hémorragiques et infectieux des ponctions. La présence d'un endométriome peut générer une augmentation du risque infectieux. # 2009 Elsevier Masson SAS. Tous droits réservés.

BACKGROUND: Approximately one in six couples experiences problems with their fertility at some point in their reproductive lives. The economic implications of the use of assisted reproductive techniques require consideration. Herein, the health economics research in this area are critically appraised. METHODS: Multiple strategies were used to identify relevant studies. Each title and abstract was independently reviewed by two members of the study team and categorized according to perceived relevance. The selected papers were then assessed for quality and data were extracted, converted to UK pounds sterling at 1999/2000 prices, tabulated and critically appraised. RESULTS: A total of 2547 papers was identified through the searches; this resulted in 30 economic evaluations, 22 cost studies and five economic benefit studies that met the selection criteria. The quality of these studies was mixed; many failed to disaggregate costs, discount future costs or conduct sensitivity analyses. Consistent findings included the following: initiating treatment with intrauterine insemination appeared to be more cost-effective than IVF; vasectomy reversal appeared to be more cost-effective than ICSI; factors associated with poor prognosis decreased the cost-effectiveness of interventions. CONCLUSIONS: The cost-effectiveness of different interventions should be considered when making decisions about treatment. Future economic appraisals of assisted reproductive techniques would benefit from more robust methodology than is evident in much of the published literature to date.

Objective: To reevaluate ovarian hyperstimulation syndrome (OHSS) prevention techniques and provide a classification system for grading OHSS and evidence-based treatment strategies for preventing OHSS. Design: A literature search was conducted in PubMed for articles published in the last 5 years using the keywords 'We reviewed randomized controlled trials (RCTs), retrospective studies, pilot studies, case studies, reviews, and meta-analyses.

Depuis les débuts de l'Assistance médicale à la procréation (AMP), la connaissance du moment de l'ovulation a toujours été une nécessité. Initialement, cette surveillance se faisait en détectant le pic urinaire de la luteinizing hormon (LH), qui permettait d'anticiper une ovulation prochaine. De nos jours, le monitorage des cycles de stimulation folliculaire est réalisé quotidiennement dans tous les centres d'AMP, en utilisant la mesure échographique du diamètre folliculaire en deux dimensions et le dosage plasmatique de l'estradiol, la progestérone et la LH plasmatique. L'ensemble de ces examens et leur répétition permettent de déterminer le nombre de follicules en croissance, d'évaluer la qualité de la réponse ovarienne (mauvaise ou hyper-répondeuse) et d'apprécier le degré de maturité folliculaire afin de choisir le moment opportun du déclenchement de l'ovulation. Le monitorage de demain se précise alors avec l'arrivée du SonoAVC, un nouveau logiciel d'exploitation des images en trois dimensions qui permet de calculer instantanément le volume de tous les follicules contenus dans un ovaire. Cette procédure est plus rapide, plus précise et possède une meilleure reproductibilité que la classique mesure manuelle du diamètre folliculaire. De plus, certaines équipes envisagent de ne monitorer les patientes qu'avec des échographies régulières en ne réalisant plus de dosages hormonaux en systématique. Après un rappel historique sur l'évolution du monitorage de l'ovulation et un état des lieux des pratiques actuelles dans les centres d'AMP, les perspectives pour le monitorage de demain seront envisagées. ß 2011 Elsevier Masson SAS. Tous droits réservés.

To critically discuss the current protocols for the management of controlled ovarian hyperstimulation in assisted reproduction technology. Design: Review of the literature and presentation of our experience. Main Outcome Measure(s): Ovarian response (peak serum estrogen levels, number of oocytes retrieved, quality of oocytes and embryos) and pregnancy outcome (clinical, delivery, and multiple pregnancy rates).

Previous studies have shown that existing antral follicles in the luteal phase enable ovarian stimulation. In a pilot study, the efficacy of double stimulations during the follicular and luteal phases in women with poor ovarian response was explored (defined according to the Bologna criteria). Thirty-eight women began with mild ovarian stimulation. After the first oocyte retrieval, human menopausal gonadotrophin and letrozole were administrated to stimulate follicle development, and oocyte retrieval was carried out a second time when dominant follicles had matured. The primary outcome measured was the number of oocytes retrieved: stage one 1.7 ± 1.0; stage two 3.5 ± 3.2. From the double stimulation, 167 oocytes were collected and 26 out of 38 (68.4%) succeeded in producing one to six viable embryos cryopreserved for later transfer. Twenty-one women underwent 23 cryopreserved embryo transfers, resulting in 13 clinical pregnancies. The study shows that double ovarian stimulations in t...

Objective: To systematically review the literature to identify randomized controlled trials, which evaluate interventions aiming to improve the probability of pregnancy in poor responders undergoing in vitro fertilization (IVF). Design: Systematic review and meta-analysis. Setting: University-based hospital. Intervention(s): None. Main Outcome Measure(s): Pregnancy rate. Result(s): Twenty-two eligible randomized controlled trials were identified that evaluated in total 15 interventions to increase pregnancy rates in poor responders. Based on limited evidence, the only interventions that appear to increase the probability of pregnancy were the addition of GH to ovarian stimulation (odds ratio for live birth: 5.22, confidence interval: 95% 1.09-24.99) and the performance of embryo transfer on day 2 compared with day 3 (ongoing pregnancy rate: 27.7% vs. 16.3%, respectively; difference: þ11.4, 95% confidence interval: þ1.6 to þ21.0). Conclusion(s): Insufficient evidence exists to recommend most of the treatments proposed to improve pregnancy rates in poor responders. Currently, there is some evidence to suggest that addition of GH, as well as performing embryo transfer on day 2 versus day 3, appear to improve the probability of pregnancy. (Fertil Steril Ò 2009;91: 749-66.

Two experiments were conducted in ewes in order to develop an oestrus-ovulation short time synchronization protocol based on combined FGA, PGF 2␣ , GnRH, eCG treatments, for use in dairy sheep before natural service (Experiment 1) or for fixed-time artificial insemination (Experiment 2), during the breeding season. In Experiment 1 seventy-five non-lactating dairy ewes were subdivided into 5 treatment groups (N = 15): (1) Group Fe -control, which received FGA vaginal sponges (14 days) + eCG (Day 14); (2) Group FPe, FGA (5 days) + PGF 2␣ (Day 5) + eCG (Day 5); (3) Group PFe, PGF 2␣ (Day 0) + FGA (5 days) + eCG (Day 5); (4) Group PFG, PGF 2␣ (Day 0) + FGA (5 days) + GnRH (30 h after sponge removal, s.r.); (5) Group GPe, GnRH (Day 0) + PGF 2␣ (Day 5) + eCG (Day 5). Ewes were checked for oestrus and hand-mated. Time of ovulation was recorded by laparoscopy for 10 animals from each treatment.

This prospective observational study aimed to assess ovarian reserve after three different methods for induction of ovulation in 60 women between 30 and 40 years old with polycystic ovary syndrome. Women were equally divided into three groups. Group I included women who responded to clomiphene citrate. Women enrolled in groups II and III were subjected to either unilateral or bilateral ovarian drilling, respectively. Ovarian reserve testing was performed once before and three months after treatment. Basal serum inhibin B level showed a significant decrease after bilateral drilling compared with predrilling level (53.8 F 13.5 vs 46.3 F 6.2 pg/mL; P ¼ 0.031). The antral follicle counts and summed ovarian volume showed a significant decrease after bilateral drilling (16.5 F 1.3 vs 14.9 F 2.1; P ¼ 0.007 and 11.5 F 1.0 vs 10.3 F 1.1/mm 3 ; P ¼ 0.001). We concluded that diminished ovarian reserve may occur after bilateral ovarian drilling but not after clomiphene citrate induction of ovulation or unilateral drilling.

Gonadotropin therapy plays an integral role in ovarian stimulation for infertility treatments. Efforts have been made over the last century to improve gonadotropin preparations. Undoubtedly, current gonadotropins have better quality and safety profiles as well as clinical efficacy than earlier ones. A major achievement has been introducing recombinant technology in the manufacturing processes for follicle-stimulating hormone, luteinizing hormone, and human chorionic gonadotropin. Recombinant gonadotropins are purer than urinederived gonadotropins, and incorporating vial filling by mass virtually eliminated batch-to-batch variations and enabled accurate dosing. Recombinant and fill-by-mass technologies have been the driving forces for launching of prefilled pen devices for more patient-friendly ovarian stimulation. The most recent developments include the fixed combination of follitropin alfa + lutropin alfa, long-acting FSH gonadotropin, and a new family of prefilled pen injector devices for administration of recombinant gonadotropins. The next step would be the production of orally bioactive molecules with selective follicle-stimulating hormone and luteinizing hormone activity.

Patients undergoing IVF/ICSI frequently experience substantial treatment burden, risk and psychological distress. These three related elements contribute to a negative patient experience that can lead to treatment discontinuation if pregnancy is not achieved. One approach to minimize these factors is the use of protocols designed to achieve high term, singleton birth rates per IVF treatment started, while improving the patient's welfare. Gonadotrophin-releasing hormone (GnRH) antagonists may be suitable for inclusion in such a protocol. In clinical trial data and meta-analyses, treatment with these agents is associated with similar live birth rates but reduced treatment burden (duration and side effects) and less risk of ovarian stimulation syndrome, compared with GnRH agonist long protocols. GnRH antagonists may also be associated with reduced psychological distress compared with agonists, but so far, the evidence for this is inconclusive. To facilitate the implementation of treatments that optimize the patient's experience, a simple GnRH antagonist protocol for use in predicted normal responders is proposed.