Hysteroscopic salpingosonography: a novel technique for infertile patients

Background: Infertility is akin to curse in our country. Patients of infertility run from pillar to post to get relief. Government Hospitals in India lie at the tail end of window-shopping of infertility centres by the patients having exhausted all their resources. Patients report without any detailed records, lost reports, coming after long hiatus of having stopped treatment in desperation, making one wonder how to proceed. At the other end are patients who have undergone laparotomy for various reasons like intestinal obstruction, tubercular abdomen, adnexal masses and their tubal status is not very clear on HSG. So, repeat laparoscopy in the former group and performing ab initio in the latter, involves putting the patients to the risk of general anesthesia, injury to internal organs due to anticipated adhesions. Although Hassan’s technique of open trocar entry is well accepted the first port entry, whatever be the mode, is an entry open to risks.Methods: In a selected group of infertile women, a baseline TVS was done on 2/3 day of menses and on the 7/8 day of menstrual cycle hysteroscopy was done which was immediately followed by another transvaginal ultrasound. The descriptive statistics is presented in the form of percentages and appropriate graphs.Results: Among the 54 patients who underwent this procedure, 65% had normal uterine cavity. 18% were referred for IVF. 9.2% conceived post procedure.Conclusions: Successive use of transvaginal ultrasound after hysteroscopy i.e Hysteroscopic sonosalpingography is a useful procedure in a select group of infertile patients.

Modified ovarian response prediction index: a novel index for ovarian response prediction in GnRH agonist cycles

Background: Evaluation of the ovarian reserve is necessary to achieve an appropriate controlled ovarian stimulation (COS). This can be done by correctly predicting the ovarian response. The objective of this study was to derive a simple index by combining the above parameters which will be helpful determining ovarian response.Methods: This retrospective analysis was performed at Guru hospital, Madurai, involving 162 patients between July 2016 and July 2018. Inclusion criteria was all patients attending for their first ICSI (intracytoplasmic sperm injection) cycle between the above period, GnRH agonist protocol as the method of ovarian stimulation, no history of any previous ovarian surgery, presence of both ovaries and no evidence of any obvious endocrine disorders. We calculated MORPI values by multiplying the AMH (ng/ml) level by the number of antral follicles (2-9 mm), and the result was divided by the age (years) of the patient and the day- 3 serum FSH level.Results: At a cut-off value of 35 (AUC-0.952) for collection of ≥ 4 oocytes and 140 (AUC-0.952) for collection of ≥ 15 oocytes, MORPI was found to have optimum sensitivity and specificity under ROC curve analysis.Conclusions: MORPI is a simple, precise and cost effective index to predict a low ovarian response, the collection of >4 MII oocytes and an excessive ovarian response in infertile women. This index also has a good ability to predict the clinical pregnancy rate. This might be used to improve the cost-benefit ratio of ovarian stimulation regimens.

Comparsion of GV oocytes transcriptome between PCOS patients and normal ovulatory women / 吉林大学学报(医学版)

Objective: To investigate the effects of controlled ovarian stimulation (COS) on the differentially expressed genes in GV oocytes and main signal transduction pathways in the polycystic ovary syndrome (PCOS) patients and the normal ovulatory women, and to screen the key genes impacting the development of oocytes of the PCOS patients. Methods: During controll ovarian hyperstimulation with GnRH-a long protocol, 3 patients with PCOS (PCOS group) and 3 normal ovulatory women due to male infertility factor (control group) were selected. Enzyme digestion was used to islolate the granule cells. The dumped immature oocytes were collected after intracytoplasmic sperm injection (ICSI). The cDNA library was constructed and sequencing was performed in Illumina MiSeq sequencing platform and RT-PCR was used to confirm the data obtained in vivo. Results: A total of 510 024 82 sequence reads were obtained, and 8 G base sequence information were contained. A total of 63 differentially expressed genes were found by bio-informatics software, including 19 significant up-regulation genes and 44 significant down-regulation genes (Fold Change>4, FDR<0. 01). The expression levels of vascular endothelial growth (VEGF) and fatly acid dehydrogenase 1 (FADS1) mRNA in the patients in PCOS group were significantly higher than those in control groups (P

Effectiveness of Gonadotropin-Releasing Hormone Antagonists in the Management of Multifollicular Recruitment in Intrauterine Insemination Cycles.

Introduction: To evaluate the efficacy of GnRH antagonists in terms of increasing the pregnancy rates in intrauterine insemination (IUI) after controlled ovarian stimulation (COS) when more than one dominant follicle is recruited. Methods: This is a prospective and randomized clinical trial that included 300 couples with primary or secondary infertility that underwent their first or second COS-IUI cycle with recombinant FSH. In all of these patients two or three leading follicles > 14 mm of mean diameter where detected by vaginal ultrasound (US) and were randomized into two groups. In group A the patients received rFSH+GnRH antagonists until the day that the hCG was given, while in group B the patients followed a standard COS received rFSH only. Results: Total amount of rFSH units (620.8+245.1vs 575.5+296.4) and clinical pregnancy rates (31.16% vs 19.15%) were statistically significantly higher in patients who were treated with GnRH antagonists. A similar number of twin pregnancies and miscarriages occurred in both groups. Conclusion: Multiple doses of GnRH antagonists in COS-IUI significantly increase pregnancy rates in multifollicular cycles.

Efficacy, efficiency and effectiveness of gonadotropin therapy for infertility treatment / Eficácia, eficiência e efetividade da terapia gonadotrófica para o tratamento da infertilidade

Gonadotropin therapy is an essential element in infertility treatments involving assisted reproductive technology. In recent years there have been outstanding advances in the development of new gonadotropins, particularly with the production of gonadotropins using biotechnological resources. Recombinant gonadotropins have higher specific activity compared with urinary counterparts, thus allowing subcutaneous administration of minimal amounts of glycoprotein. As a result, recombinant formulations have a better safety profile despite an overall similarity in terms of efficacy for pregnancy, as reported in many randomized controlled trials and meta-analyses. Gonadotropins stimulate the ovaries to develop follicles and oocytes, which are the raw material for fertilization and embryo production. The resulting embryos are transferred (fresh or frozen-thawed) to achieve pregnancy. The efficiency of a gonadotropin should therefore measured by the amount of drug used, the number of oocytes/embryos produced, and the number of pregnancies achieved by transferring fresh and/or frozen-thawed embryos to the uterus (cumulative pregnancy). Comparisons between different gonadotropin preparations should also take into account other important quality indicators in reproductive medicine, such as safety and patient-centeredeness. Altogether, the aforementioned quality indicators favor biotech gonadotropins over biologic products in infertility therapy.

RESUMO A terapia gonadotrófica é elemento essencial nos tratamentos de infertilidade que envolvem tecnologia de reprodução assistida. Nos últimos anos houve avanços notáveis no desenvolvimento de novas gonadotrofinas, principalmente com a produção de gonadotrofinas via recursos biotecnológicos. As gonadotrofinas recombinantes têm maior actividade específica em comparação com os suas homólogas urinárias, permitindo, assim, a administração subcutânea de quantidades mínimas de glicoproteína. Como resultado, as formulações recombinantes tem um melhor perfil de segurança, apesar de semelhança em termos de eficácia para a gravidez, como relatado em diversos ensaios clínicos randomizados e meta-análises. As gonadotrofinas estimulam os ovários a desenvolver folículos e ovócitos, que são a matéria-prima para a fertilização e produção de embriões. Os embriões resultantes são transferidos (frescos ou congelados/descongelados) para produzir gravidez. Comparações entre as gonadotrofinas devem, portanto, ser medidas não somente pela eficácia clínica de produzir gravidezes pela transferência de embriões a fresco, mas sobremaneira pela eficiência na produção de ovócitos e embriões em relação à quantidade de droga administrada, e efetividade na obtenção de gravidezes pela transferência de embriões frescos e congelados/descongelados (taxa de gravidez cumulativa). As comparações entre diferentes preparações de gonadotrofinas também devem levar em conta outros indicadores importantes de qualidade em medicina reprodutiva, como a segurança e o interesse do paciente. Estes indicadores de qualidade favorecem as gonadotrofinas biotecnológicas em relação aos produtos biológicos na terapia da infertilidade.

Efficacy of Random-start Controlled Ovarian Stimulation in Cancer Patients

This study aimed to evaluate the efficacy of random-start controlled ovarian stimulation (COS) in cancer patients for emergency fertility preservation. In this retrospective comparative study, 22 patients diagnosed with cancer and 44 infertile women undergoing conventional in vitro fertilization (IVF) were included. In cancer patients, ovarian stimulation was started on the day of referral, irrespective of their menstrual cycle date. The control group was selected by age matching among women undergoing conventional IVF. COS outcomes were compared between groups. The number of total and mature oocytes retrieved and the oocyte maturity rate were higher in the random-start group than in the conventional-start group. However, duration of ovarian stimulation was longer in the random-start group (11.4 vs. 10.3 days, P = 0.004). The addition of letrozole to lower the estradiol level during COS did not adversely affect total oocytes retrieved. However, oocyte maturity rate was lower in cycles with letrozole than in cycles without letrozole (71.6% vs. 58.2%, P = 0.019). Our study confirms the feasibility and effectiveness of random-start COS in cancer patients.

Efficacy of Random-start Controlled Ovarian Stimulation in Cancer Patients

This study aimed to evaluate the efficacy of random-start controlled ovarian stimulation (COS) in cancer patients for emergency fertility preservation. In this retrospective comparative study, 22 patients diagnosed with cancer and 44 infertile women undergoing conventional in vitro fertilization (IVF) were included. In cancer patients, ovarian stimulation was started on the day of referral, irrespective of their menstrual cycle date. The control group was selected by age matching among women undergoing conventional IVF. COS outcomes were compared between groups. The number of total and mature oocytes retrieved and the oocyte maturity rate were higher in the random-start group than in the conventional-start group. However, duration of ovarian stimulation was longer in the random-start group (11.4 vs. 10.3 days, P = 0.004). The addition of letrozole to lower the estradiol level during COS did not adversely affect total oocytes retrieved. However, oocyte maturity rate was lower in cycles with letrozole than in cycles without letrozole (71.6% vs. 58.2%, P = 0.019). Our study confirms the feasibility and effectiveness of random-start COS in cancer patients.

Ovarian stimulation and liver dysfunction: Is a clinical relationship possible? A case of hepatic failure after repeated cycles of ovarian stimulation / 대한생식의학회지

Liver damage induced by ovarian stimulation has been demonstrated in some cases reported in the literature. However, there has never been a fruitful debate on this topic. The present manuscript tried to fill this gap. We reported a case of a 35-year-old nulliparous woman admitted to our obstetric emergency room for severe pre-eclampsia. She had been subjected to four cycles of controlled ovarian stimulation for intrauterine insemination. At 32 weeks of gestation, she developed severe pre-eclampsia, which led to HELLP syndrome complicated by fatal liver failure. The etiological link between ovarian stimulation and HELLP syndrome is intriguing. Further investigations are needed to understand whether repeated ovarian stimulation may represent a risk factor in pre-eclamptic patients.

Effectiveness of GnRH antagonist multiple dose protocol applied during early and late follicular phase compared with GnRH agonist long protocol in non-obese and obese patients with polycystic ovary syndrome undergoing IVF/ICSI / 대한생식의학회지

OBJECTIVE: To evaluate the effectiveness of GnRH antagonist multiple dose protocol applied during early and late follicular phase (MDP-EL) in comparison with standard GnRH agonist luteal long protocol (LP) in each non-obese and obese polycystic ovary syndrome (PCOS) women undergoing IVF. METHODS: Two hundred eleven infertile women with PCOS were recruited and randomized to undergo either GnRH antagonist MDP-EL (antagonist group) or standard GnRH agonist luteal LP (agonist group). IVF cycle outcomes were compared between the two groups. RESULTS: Total dose and days of recombinant human follicle stimulating hormone (rhFSH) administered were significantly fewer in the antagonist group than in the agonist group. Incidence of severe ovarian hyperstimulation syndrome was significantly lower in the antagonist group. However, IVF and pregnancy outcomes were similar in the two groups. When all subjects were divided into non-obese and obese subgroups, in non-obese PCOS subgroup, IVF and pregnancy outcomes were comparable in the antagonist and agonist groups but total dose and days of rhFSH were also significantly fewer in the antagonist group. Similar findings were also observed in obese PCOS subgroup. CONCLUSION: GnRH antagonist MDP-EL is at least as effective as GnRH agonist LP and may be a more patient-friendly alternative in controlled ovarian stimulation for PCOS patients undergoing IVF, independent of body mass index.

Hormônio luteinizante e reprodução assistida / Assisted reproduction and luteinizing hormone

Com os avanços no conhecimento da fisiologia da foliculogênese, vários medicamentos e protocolos estão sendo desenvolvidos com o intuito de promover uma hiperestimulação ovariana controlada eficaz e segura. O uso do hormônio folículo-estimulante (FSH) recombinante nos esquemas de indução de ovulação já está bem definido e respaldado na literatura. Mais recentemente, vários estudos observaram que o hormônio luteinizante(LH) parece ter papel fundamental na maturação folicular tardia, otimizando os resultados dos esquemas de indução em determinados grupos de pacientes. Ainda não há um consenso para sua utilização rotineira e as conclusões são muitas vezes conflitantes. Este artigo visa abordar de forma objetiva o papel do LH nas técnicas de reprodução assistida, fazendo uma ampla revisão da literatura.

As folliculogenesis phisiology, several medicinal products and protocols have been developed to promote an effective and safe controlled ovarian hyperstimulation . The use of recombinant follicle-stimulating hormone (FSH) in schemes of ovulation stimulation is well defined and established in literature. More recently, several studies pointed out that luteinizing hormone seems to play a fundamental role in final stages of follicular maturation, optimizing results of induction schemes in certain groups of patients. There is no consensus about its routine use, and conclusions are often conflicting. This article aims to describe objectively the LH’s role in assisted reproduction techniques, thus offering a comprehensive review of the literature.

Disseminated intravascular coagulation developed after controlled ovarian hyperstimulation in woman with adenomyosis / 대한산부인과학회지

Disseminated intravascular coagulation (DIC) is usually developed after infection, metastatic cancer or complicated pregnancy. We experienced a case of infertile woman with adenomyosis, who had not been predisposed any common risk factors but had acute DIC during menstruation after controlled ovarian stimulation. The patient received anticoagulation therapy with supplementation of coagulation factors, followed by surgical removal of uterus 3 months later. We assumed that DIC resulted from rapidly aggravated lesion during controlled ovarian stimulation and massive intramuscular hemorrhage during menstruation. So, we report the case with brief review of literatures.