Systemic Barriers to Fertility Preservation for Sexually and Gender Diverse Populations.

Fertility preservation is the process of collecting and storing oocytes, sperm, or reproductive tissue so that a person may retain their ability to have biologically related children. In instances of infertility caused by medical intervention or an underlying medical condition, this procedure is often sought by affected patient populations. U.S. Title 21 regulations have produced disparities in access, disproportionately restricting services for sexually and gender diverse subpopulations capable of producing sperm. This article examines policies contributing to these disparities, explores how these policies may translate to real-world health care delivery, and proposes policy changes that would increase equitable access to care.

Financial decision analysis based on "willingness to pay" for surgical sperm retrieval approaches among men with non-obstructive azoospermia in the United States.

OBJECTIVE: To determine the most financially optimal surgical approach for testicular sperm retrieval for men with non-obstructive azoospermia. DESIGN: A decision tree was created examining five potential surgical approaches for men with non-obstructive azoospermia pursuing one cycle of intracytoplasmic sperm injection. An expected financial net loss was determined for each surgical option based on couples' willingness to pay for one cycle of intracytoplasmic sperm injection resulting in pregnancy. The branch with the lowest expected net loss was defined as the most optimal financial decision (minimizing loss to a couple). Fresh testicular sperm extraction implied testicular sperm extraction was performed in conjunction with programmed ovulation induction. Frozen testicular sperm extraction implied testicular sperm extraction was performed initially, and ovulation induction/intracytoplasmic sperm injection was canceled if sperm retrieval failed.  The surgical options included fresh conventional testicular sperm extraction, with and without "back-up" sperm cryopreservation, fresh microsurgical testicular sperm extraction, with and without "back-up" sperm cryopreservation, and frozen microsurgical testicular sperm extraction. Success was defined as pregnancy after one intracytoplasmic sperm injection cycle. MATERIALS AND METHODS: Probabilities of successful sperm retrieval with conventional testicular sperm extraction/microsurgical testicular sperm extraction, post-thaw sperm cellular loss following frozen microsurgical testicular sperm extraction, ovulation induction/intracytoplasmic sperm injection cycle out-of-pocket costs, intracytoplasmic sperm injection pregnancy rates for men with non-obstructive azoospermia, standard conventional testicular sperm extraction cost and average willingness to pay for intracytoplasmic sperm injection cycle were gathered from the systematic literature review. Costs were in USD and adjusted to inflation (as of April 2020). Two-way sensitivity analysis was performed on varying couples' willingness to pay for one cycle of intracytoplasmic sperm injection and varying microsurgical testicular sperm extraction out-of-pocket costs. RESULTS: According to our decision tree analysis (assuming minimum microsurgical testicular sperm extraction cost of $1,000 and willingness to pay of $8,000), the expected net loss for each branch was as follows: -$17,545 for fresh conventional testicular sperm extraction, -$17,523 for fresh microsurgical testicular sperm extraction, -$9,624 for frozen microsurgical testicular sperm extraction, -$17,991 for fresh conventional testicular sperm extraction with "backup", and -$18,210 for fresh microsurgical testicular sperm extraction with "backup". Two-way sensitivity analysis with a variable willingness to pay values and microsurgical testicular sperm extraction and in-vitro fertilization costs confirmed that frozen microsurgical testicular sperm extraction consistently presented the lowest net loss compared to other options. Interestingly, when directly comparing fresh microsurgical testicular sperm extraction and conventional testicular sperm extraction with "back-up", scenarios with decreasing willingness to pay and lower microsurgical testicular sperm extraction costs demonstrated fresh conventional testicular sperm extraction with "back-up" as more optimal than fresh microsurgical testicular sperm extraction with "back-up". CONCLUSIONS: For those couples who must pay out of pocket, our study suggests that frozen microsurgical testicular sperm extraction is the most financially optimal decision for the surgical management of non-obstructive azoospermia, regardless of microsurgical testicular sperm extraction cost and the couple's willingness to pay.

Venture capital investment in urology, 2011 to mid-2021.

INTRODUCTION: To characterize venture capital (VC) investments in urology in the past decade that represent promising innovations in early-stage companies. MATERIALS AND METHODS: A retrospective analysis of deals made between VC investors and urologic companies from January 1, 2011, through June 28, 2021, was conducted by using a financial database (PitchBook Platform, PitchBook Data Inc). Data on urologic company and investor names; company information and funding categories (surgical device, therapeutic device, drug discovery/pharmaceutical, and health care technology companies); and deal sizes (in US dollars) and dates were abstracted and aggregated. Descriptive and linear regression analyses were conducted. RESULTS: Urology-related VC funding fluctuated from 2011 through mid-2021, but no substantial change was observed in funding over time. In total, 191 distinct deals were made involving urologic companies, totaling $1.1 billion. The four largest funding categories together accounted for $848 million and comprised therapeutic devices ($373 million), surgical devices ($187 million), drug discovery/pharmaceuticals ($185 million), and health care technology ($102 million). At least $450 million (41% of total investments) was invested in companies developing minimally invasive surgical devices. CONCLUSIONS: Urologic VC investments did not increase in the past decade and were allocated more toward devices than pharmaceuticals or health care technology. Given relative patterns within urology, VC investments may shift toward health care technology and away from pharmaceuticals but remain stable for devices. Further investments in promising technologies may help urologists more effectively manage urologic disease while optimizing outcomes.

The effects of male anxiety and depression on IVF outcomes.

STUDY QUESTION: What are the effects of male anxiety and depression on IVF outcomes? SUMMARY ANSWER: Men with anxiety had lower final total motile sperm counts (fTMSC) during IVF compared to men without anxiety; however, there were no differences in live birth rates (LBRs). WHAT IS KNOWN ALREADY: Studies have shown that male anxiety causes low sperm motility, worse sperm morphology, and increased DNA fragmentation, which are known to be influential factors on fertilization rates and embryo quality during IVF. However, data are lacking on whether there is a direct association between male anxiety and/or depression and IVF outcomes. STUDY DESIGN, SIZE, DURATION: This was a survey-based, retrospective cohort study completed at a single, large hospital-affiliated fertility center with 222 respondents who underwent IVF with or without ICSI. The study was conducted between 6 September 2018 and 27 December 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Male partners of couples who underwent IVF or IVF/ICSI completed a Hospital Anxiety and Depression Scale (HADS) questionnaire. They were separated into two groups for both anxiety (HADS-A ≥ 8 or HADS-A < 8) and depression (HADS-D ≥ 8 or HADS-D < 8). Men with an elevated HADS-A or HADS-D score ≥8 were considered to have anxiety or depression, respectively. The primary outcome was LBR. Secondary outcomes included semen parameters at the time of IVF, cycle outcomes, pregnancy outcomes, and prevalence of erectile dysfunction and low libido. MAIN RESULTS AND THE ROLE OF CHANCE: There were a total of 222 respondents, of whom 22.5% had a HADS-A ≥ 8 and 6.5% had a HADS-D ≥ 8. The average age of respondents was 37.38 ± 4.90 years old. Antidepressant use was higher in the respondents with a HADS-A or HADS-D ≥ 8 (P < 0.05). Smoking use was similar between groups for both HADS-A and HADS-D (P > 0.05). When adjusted for male BMI, antidepressant use and smoking, men with a HADS-A or HADS-D ≥ 8 had similar rates of erectile dysfunction (adjusted relative risk (aRR) = 1.12 (95% CI 0.60, 2.06)) and low libido (aRR = 1.70 (95% CI 0.91, 3.15)) compared to those with a HADS-A or HADS-D ≤ 8. Men with a HADS-A ≥ 8 were more likely to have a lower fTMSC on the day of oocyte retrieval (11.8 ≥ 8 vs 20.1 < 8, adjusted ß = -0.66 (95% CI -1.22, -0.10)). However, the LBR per embryo transfer (ET) was similar between the HADS-A groups (43.2% ≥8 vs 45.1% <8, adjusted relative risk = 0.90 (95% CI 0.65, 1.06)). Although depression was uncommon in the entire cohort, the HADS-D groups were clinically similar for fTMSC (18.7 ≥ 8 vs 16.0 < 8) and LBR per ET (46.7% ≥8 vs 45.4% <8). LIMITATIONS, REASONS FOR CAUTION: Limitations of our study are the survey-based design, the lack of sperm morphology assessment at the time of IVF, our inability to fully assess the HADS-D ≥ 8 cohort due to the small sample size and the large Caucasian demographic. WIDER IMPLICATIONS OF THE FINDINGS: Couples undergoing IVF have an increased likelihood of suffering from anxiety and/or depression. There is currently a debate on whether or not men should be treated with antidepressants while attempting to conceive due to potential detrimental effects on sperm quality. Our study shows that, regardless of antidepressant use, couples with men who did or did not report anxiety and/or depression have similar LBRs when undergoing IVF. Therefore, it is important to assess both partners for mental health and to not withhold treatment due to a concern about a potential impact of antidepressants or anxiety/depression on sperm quality. STUDY FUNDING/COMPETING INTEREST(S): There was no funding to report for this study. Z.W. is a contributing author for UptoDate. S.S.S. is on the advisory board for Ferring Pharmaceuticals. E.G. was a medical consultant for Hall-Matson Esq, Teladoc, and CRICO and is a contributing author for UptoDate. The remaining authors have nothing to report. TRIAL REGISTRATION NUMBER: N/A.

Does benign prostate hyperplasia histopathological variation impact disease-specific clinical outcomes after transurethral resection?

The impact of histopathological variants in stromal and glandular tissue on clinical outcomes following transurethral resection of prostate (TURP) is unexplored. We sought to evaluate the relationship between histopathological variations in TURP specimen and postoperative clinical outcomes. We performed a retrospective analysis of men undergoing initial TURP at our institution from 2017 to 2019. All pathology slides were re-reviewed by one specialized genitourinary pathologist who was blinded to all clinical data. Types of BPH were defined as: glandular-predominant (gland:stroma ratio >50%), mixed (gland:stroma ratio 25%-50%), and stromal-predominant (gland:stromal ratio <25%). Primary clinical outcomes were ∆ post-void residual and ∆ American Urological Society Symptom Score (AUASS) at 3, 6, and 12 months post-operatively. We also evaluated for a temporal relationship between time since surgery and ∆AUASS amongst different histopathological subgroups. One hundred and five patients were included in the final analysis. 61/105 (58.1%) had glandular-predominant histopathology, 21/105 (20%) had stromal-predominant histopathology, and 23/105 (21.9%) were classified as mixed histopathology. On univariate and multivariate analysis, histopathological subtype was not a significant predictor of any of the clinical post-operative endpoints of interest at any time points. Disease-specific outcomes after TURP appear to be consistent across these different histopathologic subtypes.

Partial Component Exchange of a Non-Infected Inflatable Penile Prosthesis is Associated With a Higher Complication Rate.

OBJECTIVE: To describe the infectious and non-infectious complications in men undergoing Inflatable penile prosthesis (IPP) revision with partial and complete component exchange for mechanical malfunction. METHODS: We performed a multicenter retrospective cohort study of patients who underwent IPP revision. Men undergoing procedures for implant infection were excluded. Patients were divided into those who had complete exchange of the entire device or partial exchange of only one or 2 components. Infectious and non-infectious complications were compared between groups. RESULTS: Three hundred sixty-eight men had complete exchange of the entire device and 85 had partial component exchange. Men undergoing partial exchange had a significantly higher infection rate (7.1% vs 2.2%, P = .031). The partial exchange group also was more likely to receive antifungals (51.8 vs 16.6%, P < .001), have a modified salvage washout (77.4 vs 60.2%, P = .004), and less likely to receive vancomycin and gentamicin (63.5 vs 83.7%, P < .001). Time to revision was significantly shorter in the partial exchange group (44.9 vs 168.2 months, P < .001). Mean follow-up was slightly longer in the complete exchange group (18.3 vs 13.0 months). In multivariable analysis, partial exchange surgery, vancomycin and gentamicin prophylaxis, modified salvage washout, and antifungal prophylaxis were no longer associated with postoperative infections. The partial exchange group had greater rates of non-infectious complications (21.2% vs 9.5%, P = .005) such as pump malfunction and tubing breakage. CONCLUSION: Patients undergoing partial component revision had more infectious and non-infectious complications. These findings suggest that partial component exchange increases complications in men undergoing IPP revision.

Medical management of male infertility: now and future.

PURPOSE OF REVIEW: Medical therapy for idiopathic male infertility has historically been empiric and based on small observational studies rather than larger well designed clinical trials. This review is timely and relevant because of the recent publication of several studies that are less susceptible to bias because of being placebo-controlled and more highly powered. RECENT FINDINGS: The largest proportion of recent publications covered antioxidants, with eight randomized controlled trials (RCTs) included in this review. The Males, Antioxidants, and Infertility (MOXI) trial is of particular interest, being a large multicenter RCT, which demonstrated no improvement in semen parameters or live-birth rates with antioxidant use. In addition, phosphodiesterase-5 inhibitors (PDE5i) have been shown to improve semen parameters, while duloxetine use was not associated with any adverse effects on sperm. Progress was also made in the realm of regenerative medicine, with the realization of the first successful primate model of sperm production from pluripotent stem cells. SUMMARY: It may be time to stop recommending antioxidants for idiopathic male infertility given recent studies suggesting lack of efficacy, but given their relative safety, it is reasonable to continue their use until the evidence is overwhelming. Otherwise, stem cell therapy is another anticipated area of research interest.

Does the 5-item Frailty Index predict surgical complications of endoscopic surgical management for benign prostatic obstruction? An analysis of the ACS-NSQIP.

PURPOSE: To assess whether the 5-item Frailty Index (5i-FI) predicts surgical complications of endoscopic surgery for benign prostatic obstruction (BPO) and examine the rates of these complications across BPO surgical modalities adjusting for patient frailty. METHODS: The ACS-NSQIP registry was queried for patients who underwent transurethral resection of the prostate (TURP), photoselective vaporization of the prostate (PVP), and laser enucleation of the prostate (LEP) between 2009 and 2019. Patients' frailties were estimated using the 5i-FI. We assessed the association between 5i-FI and the following endpoints: all complications, major complications (Clavien-Dindo ≥ 3), length of stay (LOS) ≥ 2 days, and 30-day postoperative readmission. Inverse probability of treatment weighting (IPTW) was used to account for selection bias in treatment allocation. IPTW-adjusted rates for 30-day complications were compared between surgical modalities. RESULTS: The cohort included 38,399 (62.6%) TURP, 19,121 (31.2%) PVP, and 3797 (6.2%) LEP. Men with 5i-FI score ≥ 2 were more likely to receive TURP (22.7%) and PVP (22.5%) than LEP (18.8%). 5i-FI ≥ 2 was associated with higher odds of all complications (OR 1.50), major complications (OR 1.63), LOS ≥ 2 (OR 1.31), and readmission (OR 1.65). After IPTW, LEP had the lowest rates for all complications (6.29%; 95%CI 5.48-7.20), major complications (2.30%; 95%CI 1.83-2.89), and readmission (3.80%; 95%CI 3.18-4.53). CONCLUSION: The 5i-FI score is an independent predictor of 30-day postoperative surgical complications after endoscopic BPO surgery. After IPTW, LEP and PVP were associated with lower rates of complications than TURP. However, frail patients were less likely to undergo PVP and LEP. Preoperative frailty assessment could improve risk stratification before BPO surgery.

Awareness and reporting of globozoospermia among in vitro fertilization and andrology laboratories: A national survey.

Globozoospermia (GZ) is a rare disorder found in less than 0.1% of infertile men in which spermatozoa lack acrosomes necessary for penetration of an oocyte. While methods have been demonstrated to allow globozoospermic men to achieve a viable pregnancy with their partner, the Wold Health Organization considers identifying and reporting GZ on semen analysis to be 'important'. Our study aims to determine if and to what extent in vitro fertilization (IVF) laboratories nationwide recognize and report GZ on semen analysis reports. We constructed an IRB-approved survey sent nationwide to IVF and andrology clinic laboratory directors listed by the Society for Assisted Reproductive Technology and/or the American Society for Reproductive Medicine. Results from the survey were de-identified for analysis. A total of 490 surveys were sent with a response rate of 10% (n = 51). Most respondents (66%) practiced in a private, rather than academic, setting. A majority of respondents were confident in their technicians' knowledge of GZ (86%) and ability to identify it on a sample (94%). However, only half of respondents noted a space to report the concern for GZ to the ordering physician, and 25% of respondents did not feel their clinic was able to identify patients where there is a concern for GZ. Similarly, 84% of respondents did not report a percent of acrosome-deficient sperm. Less than half of respondents reported that their clinic has previously diagnosed GZ. Though the majority of respondents felt that their laboratory technicians would be able to identify GZ, a significant minority felt that their clinic did not have means to be able to report concern for GZ. This may be due to the absence of a proper channel to report a concern for GZ, a lack of knowledge about the condition, or failure to distinguish GZ from a broader reported percentage of morphologically abnormal sperm. Given evidence that the diagnosis of GZ may be under-reported in the United States, there should be a national standard for laboratory technicians to be trained to recognize GZ and be able to report their suspicion to the ordering clinician.

Optimized Use of the Electronic Health Record and Other Clinical Resources to Enhance the Management of Hypogonadal Men.

Electronic health records (EHRs) have enabled electronic documentation of a tremendous amount of clinical data. EHRs have the potential to improve communication between patients and their providers, facilitate quality improvement and outcomes research, and reduce medical errors. Conversely, EHRs have also increased clinician burnout, information clutter, and depersonalization of the interactions between patients and their providers. Increasing clinician input into EHR design, providing access to technical help, streamlining of workflow, and the use of custom templates that have fewer requirements for evaluation and management coding can reduce this burnout and increase the utility of this advancing technology.

A dietary score representing the overall relation of men's diet with semen quality in relation to outcomes of infertility treatment with assisted reproduction.

OBJECTIVE: To examine the impact of men's diet on outcomes of infertility treatment with assisted reproductive technology (ART) using an empirical score representing the relation of diet with semen quality. DESIGN: Prospective cohort study. SETTING: Fertility center at an academic medical center. PATIENTS: We included 296 men (688 semen samples) to identify an empirical dietary pattern and 231 couples (406 ART cycles) to investigate the association of this diet pattern with ART outcomes. INTERVENTIONS: Men's diet was assessed at baseline using a validated questionnaire. An empirical dietary pattern reflecting the overall relation of diet with semen quality was identified using reduced rank regression. MAIN OUTCOME MEASURES: The primary outcome was live birth per treatment cycle. The secondary outcomes were fertilization, implantation, and clinical pregnancy. RESULTS: Men had a median baseline age and body mass index of 36.8 years and 26.9 kg/m2, respectively. Although the empirical diet pattern was significantly associated with all semen parameters, the empirical diet score was not related to any clinical outcome of infertility treatment after ART. The adjusted probabilities of relevant clinical outcomes in the lowest and highest quartiles of the empirical score were 0.62 (0.50-0.73) and 0.55 (0.45-0.66) for implantation, 0.57 (0.46-0.69) and 0.50 (0.40-0.61) for clinical pregnancy, and 0.49 (0.37-0.62) and 0.36 (0.25-0.48) for live birth. Analyses excluding couples with a diagnosis of male factor infertility and, separately, excluding intracytoplasmic sperm injection cycles yielded similar results. CONCLUSIONS: A dietary score representing the overall association of diet with semen quality parameters was not associated with ART outcomes.

Secondary azoospermia after sleeve gastrectomy: a case report.

OBJECTIVE: To report the first case of secondary azoospermia after sleeve gastrectomy. DESIGN: Case report. SETTING: Academic male infertility clinic. PATIENTS: A 33-year-old man with secondary azoospermia and primary testicular failure with testosterone deficiency after laparoscopic sleeve gastrectomy. INTERVENTIONS: Hormonal therapy with anastrozole for 10 months and diagnostic testicular biopsy. MAIN OUTCOME MEASURES: Semen analyses and testicular histopathology. RESULTS: Non-obstructive azoospermia persisted at 20 months after surgery despite hormonal therapy with anastrozole. Testicular histopathology revealed the presence of Sertoli cells only. CONCLUSIONS: Although further research is need to determine the relationship between sleeve gastrectomy and secondary infertility, men should be informed of the potentially deleterious effects of this surgery on semen parameters.

Men's dietary patterns in relation to infertility treatment outcomes among couples undergoing in vitro fertilization.

PURPOSE(S): To evaluate the relationship of men's dietary patterns with outcomes of in vitro fertilization (IVF). METHODS: This is a prospective cohort study including 231 couples with 407 IVF cycles, presented at an academic fertility center from April 2007 to April 2018. We assessed diet with a validated food frequency questionnaire and identified Dietary Pattern 1 and Dietary Pattern 2 using principal component analysis. We evaluated adjusted probability of IVF outcomes across the quartiles of the adherence to two dietary patterns by generalized linear mixed models. RESULTS: Men had a median age of 36.8 years and BMI of 26.9 kg/m2. Women's median age and BMI were 35.0 years and 23.1 kg/m2, respectively. Adherence to Dietary Pattern 1 (rPearson=0.44) and Dietary Pattern 2 (rPearson=0.54) was positively correlated within couples. Adherence to Dietary Pattern 1 was positively associated with sperm concentration. A 1-unit increase in this pattern was associated with a 13.33 (0.71-25.96) million/mL higher sperm concentration. However, neither Dietary Pattern 1 nor Dietary Pattern 2 was associated with fertilization, implantation, clinical pregnancy, or live birth probabilities. CONCLUSIONS: Data-derived dietary patterns were associated with semen quality but unrelated to the probability of successful IVF outcomes.

Evaluating the quality of reported outcomes for microsurgical TESE in men with non-obstructive azoospermia: A methodological analysis.

BACKGROUND: Publications of microsurgical testicular sperm extraction (mTESE) techniques and outcomes are heterogeneous, which may limit creation of best surgical practices. OBJECTIVE: To study the quality and heterogeneity of published mTESE outcomes via a methodological analysis. MATERIALS/METHODS: A systematic methodological analysis of all published literature on the use of mTESE in men with non-obstructive azoospermia from 1999 to the July 2020 was performed. PubMed and MEDLINE searches were performed using the search terms "microdissection TESE OR microsurgical TESE." Publications were evaluated on their reporting of pre-operative factors, intraoperative techniques, surgical and clinical outcomes, and adverse events. RESULTS: Fifty-five studies met inclusion criteria. Surgical technique and sperm retrieval rates were the most reported criteria. Reporting on the presence of an embryologist intraoperatively was observed in approximately 30% of articles, while other procedural details including method of sperm quantification, quantity retrieved, and number of cryopreserved vials were observed in fewer than 10% of articles. Clinical outcomes, including pregnancy rates and live birth rates, were reported in fewer than 40% of the articles. Fetal outcomes including fetal and neonatal anomalies were rarely reported. Fetal growth restriction, preterm delivery, small or large for gestational age, and NICU admissions were never reported. CONCLUSION: There are inconsistencies in reporting quality of mTESE outcomes, specifically a lack of information on the quantity and quality of sperm retrieved, the role of embryology intraoperatively, and clinical outcomes, such as live birth rate and fetal anomalies. These gaps may guide development of standardized reporting guidelines to better assess and compare clinical outcomes across institutions and maintain focus on couples-centric fertility outcomes in future mTESE studies.

Knowledge gap across continents: the andrology and male infertility exposure among urology residents in the United States and Europe.

It is well established that resident's exposure and training are of primary importance and positively correlated with patient and health quality outcomes. We aimed to compare and contrast urology residents' self-reported perspectives and attitudes toward exposure and education of andrology and male infertility during residency in both the United States and Europe. We performed a cross-sectional design study using a survey that was distributed to a representative sample of American and European urology residents. The survey included questions regarding demographics, and the residents' perception and description of their training in this specific subspecialty. Response data were analyzed using Chi-square tests. Sixty-five percent of European and thirty-five percent American urology residents reported feeling uncomfortable in a new consultation evaluating an infertile patient and interpreting semen analyses. Surprisingly, more than half of responders replied that they would not go to their own training institutions seeking for male fertility care (78% US and 58% Europeans). In the comparative analysis, although no differences were observed in the very low number (18%) of hospitals that offer formal microsurgical training for urology residents between the US and Europe, more US institutions were reported to have an operating microscope for urology (68% vs. 41%), and more US residents replied reported participating in at least one urologic surgery using the microscope (65% vs. 34%). In conclusion, both American and European residents shared the same frustration regarding their education and exposure to andrology and male infertility during residency training. Collaborative efforts between stakeholders are needed to establish a clear and focused curriculum and training objectives to eliminate this educational gap.

Back to the basic science of fertility.

One day later, there was a marked increase in the vascular supply of the testis, and numerous vessels appeared to have breached the membrana propria of the tubules. Kochar NK, Harrison RG. The effects of x-rays on the vascularization of the mouse testis. Fertil Steril 1971;22:53-57. The impact of temperature shock upon mammalian sperm is severe, and produces physical as well as biochemical alterations in the cells. Ackerman DR. Variation due to freezing in the citrate acid content of human semen. Fertil Steril 1971;22:58-60.