The Mumbai Obstetric & Gynecological Society

The Mumbai Obstetric and Gynaecological Society www.mogsonline.org mogs

Infertility

Websites

www.asrm.org

The basic subject covered in the website of the American Society of Reproductive Medicine is fertility. It also has links to menopause medicine, andropause and endocrinology. The website has extensive literature for professionals. The highlights are the committee opinions and selected full text articles from Fertility Sterility. The patient section has comprehensive educational material in a printable format.


www.eshre.com

This European Society of Human Reproduction and Embryology website has a section on special interest groups which give useful information about subspecialty topics in infertility.


www.isarindia.net

The website of the Indian Society for Assisted Reproduction is a useful site for patients to browse through. It talks about infertility and the various therapies in general terms. It is also a useful gateway to local events.


Abstracts

Aromatase inhibitors for ovulation and pregnancy in polycystic ovary syndrome.

Ann Pharmacother. 2009 Jul;43(7):1338-46. Epub 2009 Jul 7.

Eckmann KR, Kockler DR.

Virginia Commonwealth University Health System/Medical College of Virginia Hospitals, Richmond, VA, USA.

OBJECTIVE: To evaluate evidence for use of aromatase inhibitors for ovulation induction and pregnancy in patients with polycystic ovary syndrome (PCOS).

DATA SOURCES: A MEDLINE search (1966-May 2009) was conducted using the search terms anastrozole, aromatase inhibitors, exemestane, letrozole, ovulation, and polycystic ovary syndrome to identify relevant studies.

STUDY SELECTION AND DATA EXTRACTION: Prospective clinical trials published in English and conducted in humans were identified. Trials using intrauterine insemination methods for pregnancy were excluded. The resulting articles were separated into 2 groups: aromatase inhibitor use in clomiphene-resistant patients and use in treatment-naïve patients. Eleven trials were reviewed.

DATA SYNTHESIS: Accepted pharmacologic treatments for women with PCOS and infertility include clomiphene citrate, gonadotropins, and gonadotropin-releasing hormone (GnRH) analogs. Each medication has variable efficacy rates and adverse effects. Therefore, other treatments are needed for a subset of women with PCOS and infertility. Evidence suggests that nonsteroidal aromatase inhibitors, specifically letrozole and anastrozole, may have ovulation-inducing effects by inhibiting androgen-to-estrogen conversion. Select trials with aromatase inhibitors have demonstrated efficacy for increased endometrium thickness, ovulation rates, and pregnancy rates when used in clomiphene citrate-resistant or treatment-naïve patients.

CONCLUSIONS: Further trials comparing aromatase inhibitors with clomiphene citrate are necessary before aromatase inhibitors can be recommended routinely for ovulation induction in women with PCOS and infertility. However, aromatase inhibitors may be considered in a subset of this population, specifically women who are clomiphene citrate resistant or those who, after discussion of risks and benefits, are not candidates for clomiphene citrate, gonadotropins, or GnRH analogs.


Advances in recombinant DNA technology: corifollitropin alfa, a hybrid molecule with sustained follicle-stimulating activity and reduced injection frequency.

Hum Reprod Update. 2009 May-Jun;15(3):309-21. Epub 2009 Jan 30.

Fauser BC, Mannaerts BM, Devroey P, Leader A, Boime I, Baird DT.

Department of Reproductive Medicine and Gynecology, University Medical Center, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. b.c.fauser@umcutrecht.nl

BACKGROUND: Recombinant DNA technologies have been used to develop longer-acting therapeutic proteins. One approach is to introduce sequences containing additional glycosylation sites. Using this technique, a new chimeric gene has been developed containing the coding sequences of the FSH beta-subunit and the C-terminal peptide of the hCG beta-subunit, which bears four O-linked oligosaccharide binding sites. Co-expression of the alpha-subunit and the chimeric FSH beta-subunit produces a new recombinant molecule, named corifollitropin alfa, with a prolonged elimination half-life and enhanced in vivo bioactivity compared with wild-type FSH.

METHODS: Medline searches by subject and additional searching by hand.

RESULTS: Initial studies in pituitary suppressed female volunteers confirmed the extended half-life of the compound. Phase II studies have shown that corifollitropin alfa is able to induce and sustain multi-follicular growth for an entire week in women undergoing ovarian stimulation using GnRH antagonist co-treatment for IVF. Corifollitropin alfa regimens have been developed with dosages of 100 and 150 microg, for patients with body weight 60 kg, respectively.

CONCLUSIONS: Corifollitropin alfa is the first long-acting hybrid molecule with sustained follicle-stimulating activity developed for the induction of multi-follicular growth along with GnRH antagonist co-treatment for IVF. This new treatment option may be simpler and more convenient for patients compared with conventional long protocols of daily FSH injections in combination with GnRH agonist co-treatment. The safety and efficacy of such regimens is currently being evaluated in large comparative phase III clinical trials. The development of corifollitropin alfa is the first step towards a new generation of recombinant gonadotrophins.


IVF/ICSI with or without preimplantation genetic screening for aneuploidy in couples without genetic disorders: a systematic review and meta-analysis.

J Assist Reprod Genet. 2009 May;26(5):273-83. Epub 2009 Jul 24.

Checa MA, Alonso-Coello P, Solà I, Robles A, Carreras R, Balasch J.

Department of Obstetrics and Gynecology, Hospital Universitari del Mar, Autonomous University of Barcelona, Passeig Marítim 25-29, Barcelona 08003, Spain. macheca@imas.imim.es

PURPOSE: To assess the efficacy of preimplantation genetic screening to increase ongoing pregnancy rates in couples without known genetic disorders.

METHODS: Systematic review and meta-analysis of randomized controlled trials. Two reviewers independently determined study eligibility and extracted data.

RESULTS: Ten randomized trials (1,512 women) were included. The quality of evidence was moderate. Meta-analyses using a random-effects model suggest that PGS has a lower rate of ongoing pregnancies (risk ratio=0.73, 95% confidence interval 0.62-0.87) and a lower rate of live births (risk ratio=0.76, 95% confidence interval 0.64-0.91) than standard in vitro fertilization/intracytoplasmic sperm injection.

CONCLUSIONS: In women with poor prognosis or in general in vitro fertilization program, in vitro fertilization/intracytoplasmic sperm injection with preimplantation genetic screening for aneuploidy does not increase but instead was associated with lower rates of ongoing pregnancies and live births. The use of preimplantation genetic screening in daily practice does not appear to be justified.


Improvement in sperm DNA quality using an oral antioxidant therapy.

Reprod Biomed Online. 2009 Jun;18(6):761-8.

Tunc O, Thompson J, Tremellen K.

Discipline of Obstetrics and Gynecology, University of Adelaide, South Australia.

Oxidative stress is now recognized as a common pathology that affects up to half of all infertile men. One of the principal mechanisms by which oxidative stress produces infertility is by damage to sperm DNA, either through direct oxidation of the DNA by reactive oxygen species (ROS) or by the initiation of apoptosis. The objective of this study was to determine if an oral antioxidant/mineral supplement could improve sperm DNA integrity in men with known oxidative stress. A total of 50 infertile men identified as exhibiting oxidative stress were administered oral antioxidant therapy for a period of 3 months. All participants were assessed at entry and exit for sperm DNA integrity with terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling, apoptosis with annexin V, protamination with chromomycin A(3) and ROS production with nitro blue tetrazolium assay. Sperm concentration, motility and morphology, together with assessment of serum male reproductive hormones (LH, FSH, testosterone, anti-Mullerian hormone), were also monitored. The principal finding that emerged from this study was that antioxidant therapy resulted in significant improvements in sperm DNA integrity (P = 0.002) and protamine packaging (P < 0.001), accompanied by a reduction in seminal ROS production (P = 0.027) and apoptosis (P = 0.004). No significant changes in routine sperm parameters (concentration, motility, morphology) or male reproductive hormones were observed.

 

Guideline

The Management of Ovarian Hyperstimulation Syndrome Green-top Guideline No. 5 - February 2016

 

 

Relationship Between Gonadotropin-Releasing Hormone/Gonadotropin-Releasing Hormone Receptor Signaling and Progesterone Receptors in Human Trophoblasts

Bang Hyun Lee, M.D., Ph.D., Jae Hoon Kim, M.D., Ph.D., Tae Chul Park, M.D., Ph.D., and Hee Joong Lee, M.D., Ph.D.

OBJECTIVE: To investigate the relationship between gonadotropin-releasing hormone (GnRH)/gonadotropin-releasing hormone receptor (GnRHR) signaling and progesterone receptors (PGRs).

STUDY DESIGN: HTR-8/SV neo cells and JEG-3 cells were incubated for 24 hours with GnRH-I or -II. The expression of PGRs was measured by quantitative real-time reverse transcriptase–polymerase chain reaction and Western blotting.

RESULTS: In both cells lines after incubation with 1–1,000 nM/L GnRH-I or -II the ratio of PGR-B to PGR-AB mRNA level did not differ in any of the groups as compared to the control. Relatively higher expression of PGR-B than PGR-A mRNA and expression of only PGR-B protein without PGR-A protein were observed in all specimens. There were no significant differences in the expression of PGR-B protein in each group when compared to the control group after incubation with GnRH-I or -II at 0.001–1,000 mM/L in both cell lines.

CONCLUSION: PGRs are expressed regardless of GnRH/GnRHR signaling in human trophoblasts, in which PGR-B expression is more dominant than PGR-A expression.

 

Embryo Selection for Single Embryo Transfer on Day 3 Based on Combination of Cleavage Patterns and Timing Parameters in in Vitro Fertilization Patients

Shanshan Wang, M.D., Lijun Ding, Ph.D., Xia Zhao, Ph.D., Ningyuan Zhang, M.D., Yali Hu, M.D., and Haixiang Sun, M.D.

OBJECTIVE: To evaluate whether the selection of embryos based on the combination of cleavage patterns and timing parameters using time-lapse imaging could improve the pregnancy outcomes of single embryo transfer (SET) on day 3.

STUDY DESIGN: A total of 1,728 normally fertilized and cleaved embryos were included to establish the selection criteria by using time-lapse imaging (TLI). The association of embryo cleavage patterns, timing parameters, and blastocyst quality was evaluated. Another 150 SET cycles were included in a prospective study to validate the selection criteria.

RESULTS: Embryos with normal cleavage, uneven cleavage, and nonaxial cleavage had relatively high rates of good-quality blastocysts. In addition, we identified s2 (≤0.50 h) and t5 (≤49.07 h) as the most predictive timing parameters. The strategy based on the combination of embryo cleavage patterns and timing parameters resulted in a higher good-quality blastocyst rate of 68.8%. In a prospective study, 150 SET cycles were carried out to validate the established algorithm. The clinical pregnancy rate in elective SET cycles using TLI was higher than that of SET using static morphological evaluation (75.0% vs. 47.30%).

CONCLUSION: The hierarchical strategy based on the combination of embryo cleavage patterns and timing parameters is effective for selecting the optimal embryo.

 

Use of Sperm Parameters to Predict Clinical Pregnancy with Intrauterine Insemination

Michael J. Butcher, D.O., Jabin Janoo, M.D., Mike Broce, B.A., Dara J. Seybold, M.A.A., Pickens Gantt, M.D., and Gary Randall, Ph.D.

OBJECTIVE: To test the hypothesis that morphology is the best predictor of clinical pregnancy (CP) when employing intrauterine insemination (IUI).

STUDY DESIGN: We retrospectively reviewed a registry of 527 couples who collectively underwent 1,027 IUI cycles, testing sperm parameters and other variables with univariate and multivariate analyses for association with CP. With the literature scant regarding the impact of sperm morphology on IUI outcome, we determined semen parameter threshold values in our patient population and compared them to published reference range values. A logistic regression model was used to determine predictors of CP.

RESULTS: Fecundity was 12.9% per cycle and fertility was 23.3% by the third attempted cycle. Morphology was the most significant parameter predicting CP with IUI. Motility was also significant when employing our new threshold values. Using receiver operator characteristic curve analysis, values ≥16% morphology and ≥69% motility were found to be the optimal threshold values for achieving CP.

CONCLUSION: Morphology was the best predictor of CP. When considering IUI, the best chance of clinical pregnancy occurs when both motility and morphology values are above normal thresholds.

 

Factors Affecting the Outcome of “Endometrial Scratch” in Women with Recurrent Implantation Failure

Carol Coughlan, MRCOG, MRCPI, Xi Yuan, Aygul Demirol, M.D., William Ledger, M.A., D.Phil., B.M., B.Ch., FRCOG, FRANZCOG, and Tin Chiu Li, M.D., Ph.D

OBJECTIVE: To examine factors affecting the outcome of the endometrial scratch in women with recurrent implantation failure.

STUDY DESIGN: A total of 57 eligible patients with a history of recurrent implantation failure underwent an endometrial biopsy in the luteal phase of the menstrual cycle in the month immediately preceding the embryo transfer cycle. The comparative group consisted of a retrospective cohort of 66 women with recurrent implantation failure but without endometrial biopsy. There were no significant differences between the intervention and control groups in terms of age, follicle-stimulating hormone (FSH), free androgen index, anti-Müllerian hormone, body mass index, the number of embryos transferred, and the number of embryo transfer cycles.

RESULTS: The clinical pregnancy rate in the intervention group (53%) was significantly (p<0.001) higher than that of the control group (15%). The only predictive factor was FSH. Women with FSH ≤10 IU/L had a pregnancy rate of 57.8%, significantly (p<0.05) higher than that (20%) of women with FSH >10 IU/L.

CONCLUSION: Women with a normal FSH are more likely to derive benefit from endometrial scratch.

 

Recombinant Human Luteinizing Hormone to Trigger Ovulation: Randomized, Controlled, Dose-finding Pilot Study in Ovulation Induction

Roger A. Pierson, M.S., Ph.D., Olufemi A. Olatunbosun, M.D., Donna R. Chizen, M.D., Helen Saunders, B.Sc. (Hons), Ernest Loumaye, M.D., Ph.D., and Beatrice De Moustier, M.D.

OBJECTIVE: To evaluate recombinant human luteinizing hormone (r-hLH) versus urine-derived human chorionic gonadotropin (u-hCG) to trigger ovulation in women (aged 20–40 years) with WHO Group II anovulatory infertility undergoing ovulation induction (OI) with recombinant human
follicle-stimulating hormone (r-hFSH) (150 IU/day starting dose).

STUDY DESIGN: For this Phase II, open-label, dose-finding pilot study, patients were randomized to doses of 825, 2,750, 5,500, 11,000, or 22,000 IU r-hLH or u-hCG (5,000 IU). Primary endpoints were ovulation and ratio of ruptured follicles/follicle ≥15 mm (day of r-hLH/u-hCG administration). Secondary endpoints included monofollicular ovulation and clinical pregnancy rates.

RESULTS: All 67 randomized patients completed treatment. All patients in the r-hLH 2,750 (13/13), 5,500 (12/ 12), 11,000 IU (13/13), and u-hCG 5,000 IU (12/12) groups ovulated; 3/5 patients in the r-hLH 825 IU and 2/12 in the r-hLH 22,000 IU group failed to ovulate (p=0.105 between evaluable groups). The mean ratio of ruptured follicles/ follicle ≥15 mm was 1.1 (p=0.675 between groups). The monofollicular ovulation rate was 15/60 (25%). Two cases of ovarian hyperstimulation syndrome were reported.

CONCLUSION: This open-label, pilot study (conducted in 1999–2001) suggests that the minimal effective dose of r-hLH to trigger ovulation in women with WHO Group II anovulatory infertility undergoing OI with r-hFSH (150 IU starting dose) was 2,750 IU.

 

Role of Luteal Phase Support on Gonadotropin Ovulation Induction Cycles in Patients with Polycystic Ovary Syndrome

Gurkan Yazici, M.D., Aysun Savas, M.D., Bahar Tasdelen, Ph.D., and Saffet Dilek, M.D.

OBJECTIVE: To evaluate the effect of luteal phase progesterone support on pregnancy rates in women with polycystic ovary syndrome (PCOS) who were treated for clomiphene citrate–resistant anovulatory infertility with ovulation induction and intrauterine insemination (OI/ IUI).

STUDY DESIGN: This randomized study included 110 clomiphene citrate–resistant PCOS patients. All patients underwent ovulation induction with recombinant follicle-stimulating hormone and intrauterine insemination, up to 3 cycles, and were randomized into 2 groups: (1) luteal support with progesterone or (2) a control group. The main outcomes were clinical pregnancy rates and live birth rates per cycle.

RESULTS: Demographic data were not different between the study and control groups. Cycle characteristics were found to be homogeneous between groups. A total of 38 pregnancies were achieved (15.5% pregnancy rate per cycle). The clinical pregnancy rate and live birth rate per cycle in progesterone supported cycles were 18.9% and 16.8%, respectively.

CONCLUSION: There might be a clinical benefit of luteal progesterone supplementation on OI/IUI cycles for women with PCOS. Although we did not reach a statistically significant difference between the 2 groups, luteal-supported cycles demonstrated a 6.7% higher clinical pregnancy rate and 6.1% higher live birth rate.

Top

Facebook   Twitter   Youtube   LinkedIn   Picasa

The Mumbai Obstetric & Gynecological Society

C-14, 1st Floor, Trade World, D-wing Entrance,
S. B. Marg, Kamala City, Lower Parel (W), Mumbai 400013.

Tel. : 022-24955324 / 32961841 • email: mogs2012@gmail.com

Today Visits
315

Month Visits
13351

Years Visits
144781