Progesterone receptors in AVPV kisspeptin neurons are sufficient for positive feedback induction of the LH surge

Kisspeptin, encoded by Kiss1, stimulates GnRH neurons to govern reproduction. In female rodents, estrogen-sensitive kisspeptin neurons in the rostral anteroventral periventricular (AVPV) hypothalamus are thought to mediate estradiol (E2)-induced positive feedback induction of the preovulatory luteinizing hormone (LH) surge. AVPV kisspeptin neurons co-express estrogen and progesterone receptors (PGR) and are activated during the LH surge. While E2 effects on kisspeptin neurons have been well-studied, progesterone’s regulation of kisspeptin neurons is less understood. Using transgenic mice lacking PGR exclusively in kisspeptin cells (termed KissPRKOs), we previously demonstrated that progesterone action specifically in kisspeptin cells is essential for ovulation and normal fertility. Unlike control females, KissPRKO females did not generate proper LH surges, indicating that PGR signaling in kisspeptin cells is required for proper positive feedback. However, since PGR was knocked out from all kisspeptin neurons in the brain, that study was unable to determine the specific kisspeptin population mediating PGR action on the LH surge. Here, we used targeted Cre-mediated AAV technology to re-introduce PGR selectively into AVPV kisspeptin neurons of adult KissPRKO females, and tested whether this rescues occurrence of the LH surge. We found that targeted upregulation of PGR in kisspeptin neurons exclusively in the AVPV is sufficient to restore proper E2-induced LH surges in KissPRKO females, suggesting that this specific kisspeptin population is a key target of the necessary progesterone action for the surge. These findings further highlight the critical importance of progesterone signaling, along with E2 signaling, in the positive feedback induction of LH surges and ovulation.

Outcomes of ureteroscopy and internal ureteral stent for pregnancy with urolithiasis: a systematic review and meta-analysis

Objectives To investigate the outcomes of internal ureteral stent versus ureteroscopy for pregnant women with urolithiasis. Data Sources Relevant studies published from January 1980 to April 2020 were identified through a systematic literature search in MEDLINE, EMBASE, Web of Science and Cochrane Library. Study Eligibility Criteria Total of 453 studies were initially identified. Pregnant women in any pregnancy stages who underwent D-J stent insertion only or ureteroscopy operation were included. The number of related participants in each group of study should be more than 10. This systematic review has been registered on PROSPERO (CRD42020195607). Results A total of 25 studies were identified with 131 cases serial stenting and 789 cases URS. The pooled operation success rate was 97% for D-J stent insertion, and 99% for URS. For internal ureteral stent therapy, normal fertility outcome rate was 99%, but the pooled incidence of complications was about 45%. For the URS group, normal fertility outcome rate was 99%, and the pooled incidence of complications was about 1%. However, the pooled premature and abortion incidence rate of two groups were the same as less than 1%, and same in serious complication incidence rate. Conclusions Although internal ureteral stent may cause more slight complications, ureteroscopy operation and internal ureteral stent showed less side effective on fertility results. Evidence suggests that URS therapy have greater advantage for pregnancy with urinary stones when the condition permits. As it is proved safe and effective, internal ureteral stent could be considered at emergency or other special situations.

Does last contraceptive method used impact the return of normal fertility?

Yes, according to a prospective observational study of more than 17,000 women that evaluated fecundability after stopping contraception. The authors found hormonal intrauterine device (IUD) users had slightly increased fecundability compared with users of barrier methods. There was no difference in fecundability for users of copper IUDs, implant, oral contraception, patches, rings, or natural methods compared with barrier methods. Users of injectable contraceptives experienced the longest delay in return of normal fertility, about 5 to 8 menstrual cycles.

Outcomes of ureteroscopy and internal ureteral stent for pregnancy with urolithiasis: a systematic review and meta-analysis

Objectives To investigate the outcomes of internal ureteral stent versus ureteroscopy (URS) treatments for pregnant women with urolithiasis. Design This is a systematic review and meta-analysis of observational studies that investigated the outcomes of internal ureteral stent and ureteroscopy for pregnancy with urolithiasis. This systematic review have been registered on the PROSPERO website (www.york.ac.uk/inst/crd, registration number: CRD42020195607). Data Sources Relevant studies published from January 1980 to April 2020 were identified through a systematic literature search in MEDLINE, EMBASE, Web of Science and the Cochrane Library. Data extraction and synthesis All pregnant women in their all pregnancy stages who were underwent double-J (D-J) stent insertion only or URS operation for lithotripsy/stone extraction/exploration were considered. The number of related participants in study more than 10 were included. Fertility outcome and complications of intervention were extracted as main outcomes, while other data such as operation success rate, stone free rate (SFR), patient characteristics, anaesthetic method, ureteral stone characteristics, detail of interventions were obtained as well. Complications were stratified according to Clavien-Dindo criteria. Two authors independently extracted data and assessed the quality of included studies. Study-specific prevalence rates were pooled using a random-effects model. We applied the Newcastle-Ottawa Scale quality assessment to evaluate the quality of the selected studies. Results A total of 25 studies were identified with 131 cases undergoing serial stenting and 789 cases undergoing URS operation. The age range was from 16 to 41, and urolithiasis occurred in the second trimester most. Ultrasound was the most commonly used diagnostic method. The most common site of calculi was distal ureter. The average stone size was between 6-17mm. There were 6 studies investigating D-J stent insertion only, while 23 studies involving URS operation. The most commonly used anesthesia for internal ureteral stent therapy was local anesthesia, and for URS treatments, general anesthesia and spinal anesthesia were widely used. The pooled operation success rate was 97% for D-J stent insertion, and 99% for URS. Serial D-J stenting was an effective methods for treating ureter obstruction and only a few patients passed stone spontaneously. Different common lithotripters were used in URS operations and the pooled SFR was about 91%. For internal ureteral stent therapy; the rate of normal fertility outcome was 99%, but the pooled incidence of complications was about 45%. For the URS treatment group, the rate of normal fertility outcome was 99% as well, and the pooled incidence of complications was about 1%. However, the pooled premature and abortion incidence rate of two group were the same as less than 1%, and the same as this in serious complication incidence rate. Conclusions Both ureteroscopy operation and internal ureteral stent were usually used for handing pregnancy with urolithiasis. Two treatments had less side effective on fertility outcome, but internal ureteral stent may cause more complications. Evidence suggests that URS therapy may have a greater advantage for pregnancy with urolithiasis when the conditions permit. As it is proved safe and effective, internal ureteral stent could be considered at emergency condition or preoperative preparations was lack.

Micronutrient deficiency in men with infertility

The study objective is to compare the level of micronutrients in men with infertility and men with normal fertility. Materials and methods. The levels of А, В9, D, Е, С vitamins in blood using high-performance liquid chromatography and selenium and zinc in hair using atomic absorption mass-spectrometry were measured in men with diagnosis of male idiopathic infertility (n = 82) and men with normal fertility (n = 93).Conclusion. Absence of a total lack of micronutrient deficiency in men with infertility was observed. Presumably, azoospermia can be associated with deficiency in some micronutrients casting doubt on the necessity of administration of multicomponent vitamin and mineral complexes.Results. Blood levels of А, D and В9 vitamins did not significantly differ in the studied groups, while differences in blood levels of С and Е vitamins and selenium and zinc in hair were statistically significant. While the levels of А, Е, В9 vitamins, selenium and zinc were in the reference ranges, vitamin C deficiency was observed in the test group and vitamin D deficiency in both groups. Higher level of selenium in the test group presumably reflects its higher metabolism due to higher influx of xenobiotics in the organism and indicates pre-deficiency state.

Pericentric inversion in chromosome 1 and male infertility

Pericentric inversion in chromosome 1 was thought to cause male infertility through spermatogenic impairment, regardless of the breakpoint position. However, carriers of pericentric inversion in chromosome 1 have been reported with normal fertility and familial transmission. Here, we report two cases of pericentric inversion in chromosome 1. One case was detected in utero via amniocentesis, and the other case was detected after the wife of the carrier experienced two spontaneous abortions within 5 years of marriage. Here, the effect of the breakpoint position of the inversion in chromosome 1 on male infertility is examined and compared with the published cases. The association between the breakpoint of pericentric inversion in chromosome 1 and spermatogenesis is also discussed. Overall, the results suggest that the breakpoint position deserves attention from physicians in genetic counseling as inversion carriers can produce offspring.

MicroRNA Biogenesis Machinery Is Dysregulated in the Endometrium of Infertile Women Suggesting a Role in Receptivity and Infertility

MicroRNAs (miRs) regulate endometrial function and their dysregulation could underlie unexplained infertility in women. Ribonucleases including DICER and DROSHA, and the proteins, ARGONAUTE 1 (AGO 1) and 2 (AGO 2) regulate the biogenesis/maturation of miRs. We aimed to elucidate the expression and localization of miR biogenesis machinery components during the human menstrual cycle and compare their levels in endometrium from women with normal fertility and primary unexplained infertility. miR biogenesis components were measured by quantitative-RT-PCR and immunohistochemistry. In the endometrium of women with normal fertility, DROSHA immunolocalized maximally to the epithelium during the early and mid-secretory phases compared with the proliferative and late-secretory phases. Stromal DICER immunostaining intensity was higher in the late-secretory phase compared with all other phases in fertile women. DROSHA mRNA was reduced in the mid-secretory-infertile whole endometrial tissue (has all cells of the tissue), and primary epithelial and stromal cells while no differences were found in DICER, AGO1, and AGO2 mRNA. In the luminal epithelium, DROSHA staining intensity was reduced in early and mid-secretory-infertile while DICER staining was reduced in the early secretory-infertile compared with their respective fertile groups. DICER and DROSHA were dynamically regulated across the menstrual cycle and reduced levels during receptivity phase could underlie implantation failure/infertility.