Clomiphene Citrate and Enclomiphene Hydrochloride Exposure Is Associated With Interfrontal Suture Fusion in Zebrafish

Background: The last several decades have witnessed an increase in metopic craniosynostosis incidence. Population-based studies suggest that pharmacological exposure in utero may be responsible. This study examined effects of the fertility drug clomiphene citrate (CC) on calvarial development in an established model for craniofacial development, the zebrafish Danio rerio. Results: Zebrafish larvae were exposed to clomiphene citrate or its isomer enclomiphene for five days at key points during calvarial development. Larvae were then raised to adulthood in normal rearing water. Zebrafish were analyzed using whole-mount skeletal staining. We observed differential effects on survivability, growth and suture formation depending on the treatment. Treatments with CC or enclomiphene at 5.5 mm SL led to increased fusion of the interfrontal suture (p < .01) compared to controls. Conclusions: Exposure to fertility drugs appears to affect development of the cranial vault, specifically the interfrontal suture, in zebrafish. Further research is required to identify the signaling mechanisms at play. This work suggests that fertility drug treatment may contribute to the increased incidence of metopic craniosynostosis observed globally.

The Study on Different Ovulation Induction Protocols used for Intrauterine Insemination and their Pregnancy Rate in Infertile Couples

Infertility affects millions of people of reproductive age worldwide and has an impact on their families and communities. Infertility is a disease of male or female reproductive system defined by failure to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse. Infertility is treated by different fertility drugs, ovulation induction (OI), intrauterine insemination (IUI) and in-vitro fertilization (IVF). The aim of the study is to find out the significant difference in pregnancy rate with different OI protocols used for IUI. OI is the first line treatment given to infertile women. In OI, medications are given to women for egg development and for release of eggs. OI is monitored by follicular study by ultrasonography. Semen is collected from the male partner and processed with culture media to retrieve high motile sperms, which are injected into the uterus of the female. A prospective randomized study was performed among 1343 IUI cycles. OI is started on Day 2 or Day 3 of the menstrual cycle. OI protocol is grouped according to the fertility drugs used for stimulation. The fertility drugs used for the stimulation are Clomiphene Citrate, Letrozole, Recombinant Gonadotropins, Human menopausal Gonadotropins (HMG), Human chorionic Gonadotropin (HCG). Group A uses Clomiphene citrate and HCG, Group B uses Clome, recombinant Gonadotropins and HCG. Group C uses Clome, Human menopausal Gonadotropin and HCG; Group D uses Letrozole and HCG. Group E uses Letrozole recombinant Gonadotropin and HCG. Group F used Letrozole, Human menopausal Gonadotropin and HCG. Group G used recombinant Gonadotropin and HCG. Group H used Human menopausal Gonadotropin and HCG. Group I uses only HCG. Group J was a natural cycle monitoring without any medication and was used as a control. Pregnancy rates were calculated for different age groups with different protocols. The result shows that Group B had 13% pregnancy, Group C had 9%, Group D had 3%, Group E had 10%, Group G had 11%, Group G had 11%, Group H had 7%, Group I had 4%, and Group J had 8% of pregnancy rate. The statistical analysis shows there is no significant difference with different stimulation protocols used.

Determinants of use of gonadotropin formulations to treat female infertility in an Italian region

Background Gonadotropins (Gona) are commonly used for infertility treatment in women. They are available as urinary purified extracts (u-Gona) and recombinants (r-Gona). Objectives:We investigated if socio-demographic characteristics of treated women, year of dispensation and type of prescriber may play a role in the choice of a treatment with respect to the other. Methods From administrative healthcare databases, we collected claims of Gona for women, aged 18-45, enrolled in the health care system in the year preceding the first prescription (years 2009-2018). Treatment cycles were defined as a 21-day mobile time window. We identified three groups: u-Gona, r-Gona and treatment with both formulations (m-Gona). To identify determinants, we linked women with the socio-economic position (SEP), a composite deprivation index, based on the 2011 Italian Census data,categorized in 4 levels (high, medium-high, medium-low, low). We associated prescriptions with the type of prescriber, distinguishing between specialists and general practitioners. Results We retrieved 38,598 Gona treatment cycles prescribed to 23,412 women and distributed between formulations as follows: r-Gona 47.4%, u-Gona 26.3% and m-Gona 26.3%. The median age was 38 years for r-Gona and u-Gona, 39 for m-Gona. Comparing the type of prescriber, specialists were more likely to prescribe u-Gona instead of r-Gona (OR: 2.14; 95%CI: 2.02-2.27) than general practitioners. No relation was found between SEP and Gona formulations, except for patients with the highest level who were more likely to be prescribed with r-Gona instead of u-Gona (OR: 1.12; 95%CI: 1.03-1.21). Time trends showed that treatment choices changed over time. Conclusions In the Lazio region, the choice of gonadotropin formulations varied over time and was found to be related to the prescriber and partly to socio-economic position. An analysis of outcomes related to different treatments is under way. Key messages More and more women are using artificial insemination techniques; it is important to monitor fertility drug use patterns and determinants of the choice of a treatment. The use of fertility drugs is a multifactorial phenomenon and a matter of public health interest.

Study on the mechanism of sarsasapogenin in treating precocious puberty by regulating HPG axis

Background Precocious puberty is a common endocrine disorder in children,and its pathogenic factor is early initiation of hypothalamic-pituitary-gonadal (HPG) axis. Sarsasapogenin is the main component of traditional Chinese medicine Zhimu, which has anti-fertility effect. There is already evidence that anti-fertility drugs may be resistant to precocity by regulating the HPG axis. Therefore, we speculated that sarsasapogenin might also has the effect. In order to test this hypothesis, this study determined the effect and mechanism of sarsasapogenin on precocious puberty by establishing a danazol-induced precocious puberty model. Methods Female Sprague-Dawley rats were divided into normal(N)group, model (M) group, leuprolide (L) group and sarsasapogenin (Sar) group. Rats at 5 days of age were given a single subcutaneous injection of 300 microgram of danazol dissolved in 25 microliter vehicle of ethylene glycol-ethanol (1:1, v/v), to establish the precocious puberty model. After 10 days of modeling, drug intervention was started. Vaginal opening was started at the age of 20 days, and then vaginal cell smears were examined. The development of uterus and ovary was observed by hematoxylin and eosin (HE) staining. The levels of Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol (E2) were determined by radioimmunoassay. The expressions of hypothalamic gonadotropin releasing hormone (GnRH), Kiss-1, G protein-coupled receptor 54 (GPR54) and pituitary gonadotropin releasing hormone receptor (GnRH-R) were detected by RT-PCR. Results The day of vaginal opening was significantly advanced in the M than that in the N group. Compared with the M group, the Sar and L groups could significantly delay the opening time of vaginal (P < 0.001,P < 0.05,respectively). The Sar group could significantly decrease uterine and ovarian coefficients, and reduce uterine wall thickness (P < 0.05, respectively). In terms of serum hormones (LH, FSH, E2), the M group was significantly higher than the N group (P < 0.001,respectively). Moreover, the Sar group can significantly down-regulate the levels of serum hormones (P < 0.001, P < 0.01, P < 0.01,respectively). Also, the expression of GnRH, GnRH-R, Kiss-1 mRNA were significantly decreased in the Sar group compared with that in the M group (P < 0.01, P < 0.05, P < 0.001, respectively). Conclusions The results showed that sarsasapogenin had the effect of treating precocious puberty, and its mechanism might be to down-regulate the expression of GnRH and GnRH-R mRNA through the Kiss-/GPR54 system, thus delaying the initiation of HPG axis.

Monochorionic monoamniotic live twin ectopic pregnancy: a rarity

The incidence of unilateral live twin ectopic pregnancy is approximately 1:1,25,000 but increased in last few decades due to increased use of fertility drugs for ovulation induction, superovulation and assisted reproductive technology. It is also associated with increased incidence of pelvic inflammatory diseases. Patient was 30 years old G3P2L2 who presented to OPD of this LLRM medical college, Meerut with complain of amenorrhoea of two and half months. Pelvic examination revealed tenderness in lower abdomen, left adnexal fullness and tenderness without any bleeding. On USG, left adnexal monochorionic monoamniotic ectopic twins with normal cardiac activity. Exploratory laparotomy followed by left sided salpingectomy was done and patient was discharged with satisfactory condition. This is a very rare case and PID is also among risk factors and may also cause twin ectopic pregnancy.

Getting to Adoption

Chapter 1 explores the factors that influenced couples’ decision to pursue adoption, as well as their feelings, hopes, and fears surrounding adoption. Some couples—particularly heterosexual couples—recounted years of struggling to conceive, often with the help of painful, invasive, and expensive fertility drugs and treatments. Others described genetic or medical barriers to conceiving. This chapter also addresses the kinds of circumstances, beliefs, and experiences that fostered participants’ openness to adoption as a path to parenthood. For example, having family members who were adopted enabled a basic familiarity with adoption as a family-building route, making it less “foreign” than it was to some people—and served as evidence that biogenetic ties were not prerequisites for family membership and love.